Review



human p2x3  (Azenta)

 
  • Logo
  • About
  • News
  • Press Release
  • Team
  • Advisors
  • Partners
  • Contact
  • Bioz Stars
  • Bioz vStars
    • 86
      Buy from Supplier

    Structured Review

    Azenta human p2x3
    (A, B) Overall structure (A) and cryo-EM density map (B) of the sivopixant- and ATP-bound human <t>P2X3</t> receptor viewed parallel to the membrane. Each subunit is colored distinctly. In A, the sivopixant and ATP molecules are shown in sphere representation. In B, the ligand densities are shown in gray. (C) The dolphin-shaped P2X3 subunit is colored differently according to each structural feature. The cryo-EM densities for sivopixant and ATP are shown. (D) Structure of the sivopixant- and ATP-bound human P2X3 receptor viewed perpendicular to the membrane from the extracellular side. (E) The transmembrane domain structures of the sivopixant- and ATP-bound P2X3 structure (left panel, this study) and the apo P2X3 structure (right panel, PDB ID: 5SVJ) viewed from the extracellular side. (F, G) The overall structure (F) and cryo-EM density map (G) of the ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In F, ATP molecules are shown in sphere representation, and the cryo-EM density for ATP is also shown. In G, ATP densities are shown in gray. (H) The transmembrane domain structures of the ATP-bound P2X3 structure (this study, left panel), the desensitized P2X3 structure (middle panel, PDB ID: 5SVL), and the open P2X3 structure (right panel, PDB ID: 5SVK) viewed from the extracellular side.
    Human P2x3, supplied by Azenta, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/human p2x3/product/Azenta
    Average 86 stars, based on 1 article reviews
    human p2x3 - by Bioz Stars, 2026-06
    86/100 stars

    Images

    1) Product Images from "Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor"

    Article Title: Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

    Journal: bioRxiv

    doi: 10.64898/2026.01.03.697462

    (A, B) Overall structure (A) and cryo-EM density map (B) of the sivopixant- and ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In A, the sivopixant and ATP molecules are shown in sphere representation. In B, the ligand densities are shown in gray. (C) The dolphin-shaped P2X3 subunit is colored differently according to each structural feature. The cryo-EM densities for sivopixant and ATP are shown. (D) Structure of the sivopixant- and ATP-bound human P2X3 receptor viewed perpendicular to the membrane from the extracellular side. (E) The transmembrane domain structures of the sivopixant- and ATP-bound P2X3 structure (left panel, this study) and the apo P2X3 structure (right panel, PDB ID: 5SVJ) viewed from the extracellular side. (F, G) The overall structure (F) and cryo-EM density map (G) of the ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In F, ATP molecules are shown in sphere representation, and the cryo-EM density for ATP is also shown. In G, ATP densities are shown in gray. (H) The transmembrane domain structures of the ATP-bound P2X3 structure (this study, left panel), the desensitized P2X3 structure (middle panel, PDB ID: 5SVL), and the open P2X3 structure (right panel, PDB ID: 5SVK) viewed from the extracellular side.
    Figure Legend Snippet: (A, B) Overall structure (A) and cryo-EM density map (B) of the sivopixant- and ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In A, the sivopixant and ATP molecules are shown in sphere representation. In B, the ligand densities are shown in gray. (C) The dolphin-shaped P2X3 subunit is colored differently according to each structural feature. The cryo-EM densities for sivopixant and ATP are shown. (D) Structure of the sivopixant- and ATP-bound human P2X3 receptor viewed perpendicular to the membrane from the extracellular side. (E) The transmembrane domain structures of the sivopixant- and ATP-bound P2X3 structure (left panel, this study) and the apo P2X3 structure (right panel, PDB ID: 5SVJ) viewed from the extracellular side. (F, G) The overall structure (F) and cryo-EM density map (G) of the ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In F, ATP molecules are shown in sphere representation, and the cryo-EM density for ATP is also shown. In G, ATP densities are shown in gray. (H) The transmembrane domain structures of the ATP-bound P2X3 structure (this study, left panel), the desensitized P2X3 structure (middle panel, PDB ID: 5SVL), and the open P2X3 structure (right panel, PDB ID: 5SVK) viewed from the extracellular side.

    Techniques Used: Cryo-EM Sample Prep, Membrane

    (A) Overall structure of the sivopixant- and ATP-bound human P2X3 receptor (upper-left panel) and a close-up view of the sivopixant binding site (lower-left panel) viewed perpendicular to the membrane from the extracellular side. Close-up views of the sivopixant binding site are shown from two different angles (upper-right and lower-right panels). The ligand molecules and amino acid residues involved in sivopixant binding are shown in stick representation. Dotted lines represent hydrogen bonds. (B) Schematic diagram of the interactions between P2X3 and sivopixant. Dotted lines represent hydrogen bonds. (C) Amino acid sequence alignment of P2X3 receptors from Mus musculus (Q3UR32.1), Rattus norvegicus (P49654.1), Canis familiaris (XP_038280235.1), Bos taurus (XP_059731161.1), Gallus gallus (NP_001384137.1), and Danio rerio (NP_571698.3); P2X receptors from Homo sapiens (P2X1: P51575.1; P2X2: Q9UBL9.1; P2X3: P56373.2; P2X4: Q99571.2; P2X5: Q93086.4; P2X6: O15547.2; and P2X7: Q99572.4) as well as the Mus musculus P2X2 receptor (Q8K3P1.2) and Rattus norvegicus P2X2 receptor (CAA71046.1). The residues involved in sivopixant binding are shown. The blue circles indicate the residues shown in B.
    Figure Legend Snippet: (A) Overall structure of the sivopixant- and ATP-bound human P2X3 receptor (upper-left panel) and a close-up view of the sivopixant binding site (lower-left panel) viewed perpendicular to the membrane from the extracellular side. Close-up views of the sivopixant binding site are shown from two different angles (upper-right and lower-right panels). The ligand molecules and amino acid residues involved in sivopixant binding are shown in stick representation. Dotted lines represent hydrogen bonds. (B) Schematic diagram of the interactions between P2X3 and sivopixant. Dotted lines represent hydrogen bonds. (C) Amino acid sequence alignment of P2X3 receptors from Mus musculus (Q3UR32.1), Rattus norvegicus (P49654.1), Canis familiaris (XP_038280235.1), Bos taurus (XP_059731161.1), Gallus gallus (NP_001384137.1), and Danio rerio (NP_571698.3); P2X receptors from Homo sapiens (P2X1: P51575.1; P2X2: Q9UBL9.1; P2X3: P56373.2; P2X4: Q99571.2; P2X5: Q93086.4; P2X6: O15547.2; and P2X7: Q99572.4) as well as the Mus musculus P2X2 receptor (Q8K3P1.2) and Rattus norvegicus P2X2 receptor (CAA71046.1). The residues involved in sivopixant binding are shown. The blue circles indicate the residues shown in B.

    Techniques Used: Binding Assay, Membrane, Sequencing

    (A) Representative current traces of the effects of sivopixant on human P2X3 currents at different ATP concentrations. (B) Effects of sivopixant on ATP (0.1, 1 and 10 µM)-evoked currents of human P2X3 (mean ± SEM, n = 3-4). (C, E) Representative current traces of sivopixant effects at 1 μM (C) and 0.3 μM (E) on ATP-evoked currents of human P2X3 and its mutants (C: M96W, M165W, and Y285W; E: T82I). (D, F) Effects of 1 μM (D) and 0.3 μM (F) sivopixant on the ATP-evoked currents of human P2X3 and its mutants (mean ± SEM, n = 3-5). Two-way ANOVA followed by Tukey‘s multiple comparisons test (B) and one-side one-way ANOVA followed by post hoc test (D, F), **p < 0.01, ****p < 0.0001 vs. WT). The hP2X3 WT data shown in and were obtained from the same cells and are shown in the respective panels for comparison.
    Figure Legend Snippet: (A) Representative current traces of the effects of sivopixant on human P2X3 currents at different ATP concentrations. (B) Effects of sivopixant on ATP (0.1, 1 and 10 µM)-evoked currents of human P2X3 (mean ± SEM, n = 3-4). (C, E) Representative current traces of sivopixant effects at 1 μM (C) and 0.3 μM (E) on ATP-evoked currents of human P2X3 and its mutants (C: M96W, M165W, and Y285W; E: T82I). (D, F) Effects of 1 μM (D) and 0.3 μM (F) sivopixant on the ATP-evoked currents of human P2X3 and its mutants (mean ± SEM, n = 3-5). Two-way ANOVA followed by Tukey‘s multiple comparisons test (B) and one-side one-way ANOVA followed by post hoc test (D, F), **p < 0.01, ****p < 0.0001 vs. WT). The hP2X3 WT data shown in and were obtained from the same cells and are shown in the respective panels for comparison.

    Techniques Used: Comparison

    (A-F) Close-up views of the sivopixant binding site of the sivopixant- and ATP-bound P2X3 structure (in this study, yellow and blue). The human P2X1 structure (PDB ID: 9C2A) (A), the human P2X2 structure (PDB ID: 9DDV) (B), the human P2X4 structure (PDB ID: 9BQH) (C), the human P2X7 structure (PDB ID: 9E3M) (D), and the predicted heterotrimer structure formed by two P2X2 subunits and one P2X3 subunit (AlphaFold3, ipTM=0.71) (E, F) are superposed onto the P2X3 structure and shown in gray. In E, the gray chain superposed onto the yellow chain is the P2X2 subunit, while the gray chain superposed onto the blue chain is the P2X3 subunit. In F, the gray chain superposed onto the yellow chain is the P2X3 subunit, while the gray chain superposed onto the blue chain is the P2X2 subunit.
    Figure Legend Snippet: (A-F) Close-up views of the sivopixant binding site of the sivopixant- and ATP-bound P2X3 structure (in this study, yellow and blue). The human P2X1 structure (PDB ID: 9C2A) (A), the human P2X2 structure (PDB ID: 9DDV) (B), the human P2X4 structure (PDB ID: 9BQH) (C), the human P2X7 structure (PDB ID: 9E3M) (D), and the predicted heterotrimer structure formed by two P2X2 subunits and one P2X3 subunit (AlphaFold3, ipTM=0.71) (E, F) are superposed onto the P2X3 structure and shown in gray. In E, the gray chain superposed onto the yellow chain is the P2X2 subunit, while the gray chain superposed onto the blue chain is the P2X3 subunit. In F, the gray chain superposed onto the yellow chain is the P2X3 subunit, while the gray chain superposed onto the blue chain is the P2X2 subunit.

    Techniques Used: Binding Assay

    (A) Representative current traces of the effects of sivopixant on ATP-evoked currents of human P2X3 wild type (WT) and its gain-of-function mutant (GOF). (B) Effects of sivopixant on ATP-evoked currents of human P2X3 and its mutant (mean ± SEM, n = 3-4). (One-way ANOVA followed by Tukey‘s multiple comparisons test, ***p < 0.001 hP2X1GOF vs. hP2X1-WT, ****p < 0.0001 hP2X2GOF vs. hP2X2-WT). The hP2X3 WT data shown in and were obtained from the same cells and are shown in the respective panels for comparison.
    Figure Legend Snippet: (A) Representative current traces of the effects of sivopixant on ATP-evoked currents of human P2X3 wild type (WT) and its gain-of-function mutant (GOF). (B) Effects of sivopixant on ATP-evoked currents of human P2X3 and its mutant (mean ± SEM, n = 3-4). (One-way ANOVA followed by Tukey‘s multiple comparisons test, ***p < 0.001 hP2X1GOF vs. hP2X1-WT, ****p < 0.0001 hP2X2GOF vs. hP2X2-WT). The hP2X3 WT data shown in and were obtained from the same cells and are shown in the respective panels for comparison.

    Techniques Used: Mutagenesis, Comparison

    (A) Superimposition of the sivopixant- and ATP-bound P2X3 structure (in this study, blue) and the ATP-bound, open P2X3 structure (PDB ID: 5SVK, red) onto the apo, closed P2X3 structure (PDB ID: 5SVJ, gray) viewed parallel to the membrane. Close-up views of the dorsal fin, left flipper, and lower body domains are also shown. The arrows indicate conformational changes in the open P2X3 structure (red) and the sivopixant- and ATP-bound P2X3 structure (blue). (B, C) Close-up view of the ATP binding site of the sivopixant- and ATP-bound P2X3 structure (in this study, blue) (B) and the open P2X3 structure (PDB ID: 5SVK, red) (C). The ATP molecules and amino acid residues involved in ATP binding are shown in stick representation. Dotted lines represent hydrogen bonds. (D, E) Superimposition of the open P2X3 structure (PDB ID: 5SVK, red) (D) and the sivopixant- and ATP-bound P2X3 structure (this study, blue) (E) onto the apo P2X3 structure (PDB ID: 5SVJ, gray). Only the transmembrane and body domains from the two subunits in the foreground are shown.
    Figure Legend Snippet: (A) Superimposition of the sivopixant- and ATP-bound P2X3 structure (in this study, blue) and the ATP-bound, open P2X3 structure (PDB ID: 5SVK, red) onto the apo, closed P2X3 structure (PDB ID: 5SVJ, gray) viewed parallel to the membrane. Close-up views of the dorsal fin, left flipper, and lower body domains are also shown. The arrows indicate conformational changes in the open P2X3 structure (red) and the sivopixant- and ATP-bound P2X3 structure (blue). (B, C) Close-up view of the ATP binding site of the sivopixant- and ATP-bound P2X3 structure (in this study, blue) (B) and the open P2X3 structure (PDB ID: 5SVK, red) (C). The ATP molecules and amino acid residues involved in ATP binding are shown in stick representation. Dotted lines represent hydrogen bonds. (D, E) Superimposition of the open P2X3 structure (PDB ID: 5SVK, red) (D) and the sivopixant- and ATP-bound P2X3 structure (this study, blue) (E) onto the apo P2X3 structure (PDB ID: 5SVJ, gray). Only the transmembrane and body domains from the two subunits in the foreground are shown.

    Techniques Used: Membrane, Binding Assay

    (A) Close-up view of the sivopixant binding site of the P2X3 receptor. Superimposition of the sivopixant- and ATP-bound P2X3 structure (this study, blue) and the open P2X3 structure (PDB ID: 5SVK, red) onto the apo P2X3 structure (PDB ID: 5SVJ, gray) viewed perpendicular to the membrane from the extracellular side. Dotted lines indicate the distance (Å) between the Cα atoms of Glu289 in two adjacent subunits. (B-E) MD simulations using the sivopixant- and ATP-bound structure with both retained (B), ATP deleted (C), sivopixant deleted (D) and both deleted (E) as starting models. The distance plots of Cα atoms between Glu289 of two adjacent subunits are shown. The average distances in the trimer are shown.
    Figure Legend Snippet: (A) Close-up view of the sivopixant binding site of the P2X3 receptor. Superimposition of the sivopixant- and ATP-bound P2X3 structure (this study, blue) and the open P2X3 structure (PDB ID: 5SVK, red) onto the apo P2X3 structure (PDB ID: 5SVJ, gray) viewed perpendicular to the membrane from the extracellular side. Dotted lines indicate the distance (Å) between the Cα atoms of Glu289 in two adjacent subunits. (B-E) MD simulations using the sivopixant- and ATP-bound structure with both retained (B), ATP deleted (C), sivopixant deleted (D) and both deleted (E) as starting models. The distance plots of Cα atoms between Glu289 of two adjacent subunits are shown. The average distances in the trimer are shown.

    Techniques Used: Binding Assay, Membrane

    Cartoon diagrams illustrating the conformational changes of P2X3 from the apo state (middle) to the ATP-bound, open state (left) and the sivopixant- and ATP-bound, closed state (right). The arrows indicate conformational changes between two states.
    Figure Legend Snippet: Cartoon diagrams illustrating the conformational changes of P2X3 from the apo state (middle) to the ATP-bound, open state (left) and the sivopixant- and ATP-bound, closed state (right). The arrows indicate conformational changes between two states.

    Techniques Used:



    Similar Products

    human p2x3  (Azenta)
    86
    Azenta human p2x3
    (A, B) Overall structure (A) and cryo-EM density map (B) of the sivopixant- and ATP-bound human <t>P2X3</t> receptor viewed parallel to the membrane. Each subunit is colored distinctly. In A, the sivopixant and ATP molecules are shown in sphere representation. In B, the ligand densities are shown in gray. (C) The dolphin-shaped P2X3 subunit is colored differently according to each structural feature. The cryo-EM densities for sivopixant and ATP are shown. (D) Structure of the sivopixant- and ATP-bound human P2X3 receptor viewed perpendicular to the membrane from the extracellular side. (E) The transmembrane domain structures of the sivopixant- and ATP-bound P2X3 structure (left panel, this study) and the apo P2X3 structure (right panel, PDB ID: 5SVJ) viewed from the extracellular side. (F, G) The overall structure (F) and cryo-EM density map (G) of the ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In F, ATP molecules are shown in sphere representation, and the cryo-EM density for ATP is also shown. In G, ATP densities are shown in gray. (H) The transmembrane domain structures of the ATP-bound P2X3 structure (this study, left panel), the desensitized P2X3 structure (middle panel, PDB ID: 5SVL), and the open P2X3 structure (right panel, PDB ID: 5SVK) viewed from the extracellular side.
    Human P2x3, supplied by Azenta, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/human p2x3/product/Azenta
    Average 86 stars, based on 1 article reviews
    human p2x3 - by Bioz Stars, 2026-06
    86/100 stars
    		  Buy from Supplier
    human p2x3 receptor  (Biomol GmbH)
    90
    Biomol GmbH human p2x3 receptor
    (A, B) Overall structure (A) and cryo-EM density map (B) of the sivopixant- and ATP-bound human <t>P2X3</t> receptor viewed parallel to the membrane. Each subunit is colored distinctly. In A, the sivopixant and ATP molecules are shown in sphere representation. In B, the ligand densities are shown in gray. (C) The dolphin-shaped P2X3 subunit is colored differently according to each structural feature. The cryo-EM densities for sivopixant and ATP are shown. (D) Structure of the sivopixant- and ATP-bound human P2X3 receptor viewed perpendicular to the membrane from the extracellular side. (E) The transmembrane domain structures of the sivopixant- and ATP-bound P2X3 structure (left panel, this study) and the apo P2X3 structure (right panel, PDB ID: 5SVJ) viewed from the extracellular side. (F, G) The overall structure (F) and cryo-EM density map (G) of the ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In F, ATP molecules are shown in sphere representation, and the cryo-EM density for ATP is also shown. In G, ATP densities are shown in gray. (H) The transmembrane domain structures of the ATP-bound P2X3 structure (this study, left panel), the desensitized P2X3 structure (middle panel, PDB ID: 5SVL), and the open P2X3 structure (right panel, PDB ID: 5SVK) viewed from the extracellular side.
    Human P2x3 Receptor, supplied by Biomol GmbH, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/human p2x3 receptor/product/Biomol GmbH
    Average 90 stars, based on 1 article reviews
    human p2x3 receptor - by Bioz Stars, 2026-06
    90/100 stars
    		  Buy from Supplier
    human p2x2, p2x3 and p2x2/3 1321n1 stable cells  (Afferent Pharmaceuticals)
    90
    Afferent Pharmaceuticals human p2x2, p2x3 and p2x2/3 1321n1 stable cells
    (A, B) Overall structure (A) and cryo-EM density map (B) of the sivopixant- and ATP-bound human <t>P2X3</t> receptor viewed parallel to the membrane. Each subunit is colored distinctly. In A, the sivopixant and ATP molecules are shown in sphere representation. In B, the ligand densities are shown in gray. (C) The dolphin-shaped P2X3 subunit is colored differently according to each structural feature. The cryo-EM densities for sivopixant and ATP are shown. (D) Structure of the sivopixant- and ATP-bound human P2X3 receptor viewed perpendicular to the membrane from the extracellular side. (E) The transmembrane domain structures of the sivopixant- and ATP-bound P2X3 structure (left panel, this study) and the apo P2X3 structure (right panel, PDB ID: 5SVJ) viewed from the extracellular side. (F, G) The overall structure (F) and cryo-EM density map (G) of the ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In F, ATP molecules are shown in sphere representation, and the cryo-EM density for ATP is also shown. In G, ATP densities are shown in gray. (H) The transmembrane domain structures of the ATP-bound P2X3 structure (this study, left panel), the desensitized P2X3 structure (middle panel, PDB ID: 5SVL), and the open P2X3 structure (right panel, PDB ID: 5SVK) viewed from the extracellular side.
    Human P2x2, P2x3 And P2x2/3 1321n1 Stable Cells, supplied by Afferent Pharmaceuticals, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/human p2x2, p2x3 and p2x2/3 1321n1 stable cells/product/Afferent Pharmaceuticals
    Average 90 stars, based on 1 article reviews
    human p2x2, p2x3 and p2x2/3 1321n1 stable cells - by Bioz Stars, 2026-06
    90/100 stars
    		  Buy from Supplier
    human pegfp-c1-p2x3 plasmid  (Thermo Fisher)
    90
    Thermo Fisher human pegfp-c1-p2x3 plasmid
    (A, B) Overall structure (A) and cryo-EM density map (B) of the sivopixant- and ATP-bound human <t>P2X3</t> receptor viewed parallel to the membrane. Each subunit is colored distinctly. In A, the sivopixant and ATP molecules are shown in sphere representation. In B, the ligand densities are shown in gray. (C) The dolphin-shaped P2X3 subunit is colored differently according to each structural feature. The cryo-EM densities for sivopixant and ATP are shown. (D) Structure of the sivopixant- and ATP-bound human P2X3 receptor viewed perpendicular to the membrane from the extracellular side. (E) The transmembrane domain structures of the sivopixant- and ATP-bound P2X3 structure (left panel, this study) and the apo P2X3 structure (right panel, PDB ID: 5SVJ) viewed from the extracellular side. (F, G) The overall structure (F) and cryo-EM density map (G) of the ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In F, ATP molecules are shown in sphere representation, and the cryo-EM density for ATP is also shown. In G, ATP densities are shown in gray. (H) The transmembrane domain structures of the ATP-bound P2X3 structure (this study, left panel), the desensitized P2X3 structure (middle panel, PDB ID: 5SVL), and the open P2X3 structure (right panel, PDB ID: 5SVK) viewed from the extracellular side.
    Human Pegfp C1 P2x3 Plasmid, supplied by Thermo Fisher, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/human pegfp-c1-p2x3 plasmid/product/Thermo Fisher
    Average 90 stars, based on 1 article reviews
    human pegfp-c1-p2x3 plasmid - by Bioz Stars, 2026-06
    90/100 stars
    		  Buy from Supplier
    cells 1321n1 astrocytoma lines stably transfected with human p2x2, p2x3, or co-expressing p2x2 and p2x3 receptors  (Afferent Pharmaceuticals)
    90
    Afferent Pharmaceuticals cells 1321n1 astrocytoma lines stably transfected with human p2x2, p2x3, or co-expressing p2x2 and p2x3 receptors
    MK‐7264 antagonism of human <t>P2X3</t> receptor is associated with an onset of slowed desensitisation. (a) Representative trace showing a diminished peak response and appearance of slow desensitisation are associated with MK‐7264 antagonism. (b) Representative superimposed trace showing time‐dependent recovery of P2X3 fast desensitisation following MK‐7264 (300 nM) wash‐off. Agonist applied every 4 min. (c) Relationship between MK‐7264 concentration and the rate of desensitisation. Time constants (τ values) were derived from single exponential curves fitted to the desensitisation phase 250–750 ms after the peak response. The τ values were compared with a Kruskal–Wallis ANOVA (P < .05) followed by Dunn's post hoc test; N = 6. (d) The change in shape of the current following MK‐7264 antagonism quantified as a fractional response (residual current, 1 s after onset of agonist response over peak current) and compared with a Kruskal–Wallis ANOVA followed by Dunn's post hoc test. *P < 0.05 versus control response; N = 7
    Cells 1321n1 Astrocytoma Lines Stably Transfected With Human P2x2, P2x3, Or Co Expressing P2x2 And P2x3 Receptors, supplied by Afferent Pharmaceuticals, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/cells 1321n1 astrocytoma lines stably transfected with human p2x2, p2x3, or co-expressing p2x2 and p2x3 receptors/product/Afferent Pharmaceuticals
    Average 90 stars, based on 1 article reviews
    cells 1321n1 astrocytoma lines stably transfected with human p2x2, p2x3, or co-expressing p2x2 and p2x3 receptors - by Bioz Stars, 2026-06
    90/100 stars
    		  Buy from Supplier
    1321n1 astrocytoma lines stably transfected with human p2x2, p2x3, or co-expressing p2x2 and p2x3 receptors  (Afferent Pharmaceuticals)
    90
    Afferent Pharmaceuticals 1321n1 astrocytoma lines stably transfected with human p2x2, p2x3, or co-expressing p2x2 and p2x3 receptors
    MK‐7264 antagonism of human <t>P2X3</t> receptor is associated with an onset of slowed desensitisation. (a) Representative trace showing a diminished peak response and appearance of slow desensitisation are associated with MK‐7264 antagonism. (b) Representative superimposed trace showing time‐dependent recovery of P2X3 fast desensitisation following MK‐7264 (300 nM) wash‐off. Agonist applied every 4 min. (c) Relationship between MK‐7264 concentration and the rate of desensitisation. Time constants (τ values) were derived from single exponential curves fitted to the desensitisation phase 250–750 ms after the peak response. The τ values were compared with a Kruskal–Wallis ANOVA (P < .05) followed by Dunn's post hoc test; N = 6. (d) The change in shape of the current following MK‐7264 antagonism quantified as a fractional response (residual current, 1 s after onset of agonist response over peak current) and compared with a Kruskal–Wallis ANOVA followed by Dunn's post hoc test. *P < 0.05 versus control response; N = 7
    1321n1 Astrocytoma Lines Stably Transfected With Human P2x2, P2x3, Or Co Expressing P2x2 And P2x3 Receptors, supplied by Afferent Pharmaceuticals, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/1321n1 astrocytoma lines stably transfected with human p2x2, p2x3, or co-expressing p2x2 and p2x3 receptors/product/Afferent Pharmaceuticals
    Average 90 stars, based on 1 article reviews
    1321n1 astrocytoma lines stably transfected with human p2x2, p2x3, or co-expressing p2x2 and p2x3 receptors - by Bioz Stars, 2026-06
    90/100 stars
    		  Buy from Supplier
    human pcdna3.0-egfp- p2x3 plasmid  (Thermo Fisher)
    90
    Thermo Fisher human pcdna3.0-egfp- p2x3 plasmid
    MK‐7264 antagonism of human <t>P2X3</t> receptor is associated with an onset of slowed desensitisation. (a) Representative trace showing a diminished peak response and appearance of slow desensitisation are associated with MK‐7264 antagonism. (b) Representative superimposed trace showing time‐dependent recovery of P2X3 fast desensitisation following MK‐7264 (300 nM) wash‐off. Agonist applied every 4 min. (c) Relationship between MK‐7264 concentration and the rate of desensitisation. Time constants (τ values) were derived from single exponential curves fitted to the desensitisation phase 250–750 ms after the peak response. The τ values were compared with a Kruskal–Wallis ANOVA (P < .05) followed by Dunn's post hoc test; N = 6. (d) The change in shape of the current following MK‐7264 antagonism quantified as a fractional response (residual current, 1 s after onset of agonist response over peak current) and compared with a Kruskal–Wallis ANOVA followed by Dunn's post hoc test. *P < 0.05 versus control response; N = 7
    Human Pcdna3.0 Egfp P2x3 Plasmid, supplied by Thermo Fisher, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/human pcdna3.0-egfp- p2x3 plasmid/product/Thermo Fisher
    Average 90 stars, based on 1 article reviews
    human pcdna3.0-egfp- p2x3 plasmid - by Bioz Stars, 2026-06
    90/100 stars
    		  Buy from Supplier
    human pcdna3.0-egfp-p2x3 plasmid  (Thermo Fisher)
    90
    Thermo Fisher human pcdna3.0-egfp-p2x3 plasmid
    Effect of nano emodin on the expression of <t>P2X3</t> mRNA and protein in the DRG of T2DM rats. a. Expression of P2X3 mRNA was examined using real time RT-PCR. Expression levels of P2X3 mRNA in the T2DM group were higher than in the control group (p < 0.05, n = 8 for each group). Levels of P2X3 mRNA in T2DM rats treated with nano emodin were significantly lower than in the untreated T2DM group (p < 0.05, n = 8 for each group). There were no differences in expression levels of P2X3 mRNA when comparing the DRG from the DM group and DM + nanocarrier group (p > 0.05, n = 8 for each group). Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group. b. The expression of P2X3 protein in the DRG was examined using Western blots. Image analysis revealed that levels (assessed by integrated optical density) of P2X3 protein (normalized to each β-actin internal control) in the DM group were higher than in the control group. Levels of P2X3 protein in T2DM rats treated with nano emodin were significantly lower than in the DM group. There were no differences in the levels of P2X3 protein when comparing DRG from the DM group and DM + nanocarrier group. Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group
    Human Pcdna3.0 Egfp P2x3 Plasmid, supplied by Thermo Fisher, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/human pcdna3.0-egfp-p2x3 plasmid/product/Thermo Fisher
    Average 90 stars, based on 1 article reviews
    human pcdna3.0-egfp-p2x3 plasmid - by Bioz Stars, 2026-06
    90/100 stars
    		  Buy from Supplier
    recombinant human or rat p2x3 receptors  (Pfizer Inc)
    90
    Pfizer Inc recombinant human or rat p2x3 receptors
    Effect of nano emodin on the expression of <t>P2X3</t> mRNA and protein in the DRG of T2DM rats. a. Expression of P2X3 mRNA was examined using real time RT-PCR. Expression levels of P2X3 mRNA in the T2DM group were higher than in the control group (p < 0.05, n = 8 for each group). Levels of P2X3 mRNA in T2DM rats treated with nano emodin were significantly lower than in the untreated T2DM group (p < 0.05, n = 8 for each group). There were no differences in expression levels of P2X3 mRNA when comparing the DRG from the DM group and DM + nanocarrier group (p > 0.05, n = 8 for each group). Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group. b. The expression of P2X3 protein in the DRG was examined using Western blots. Image analysis revealed that levels (assessed by integrated optical density) of P2X3 protein (normalized to each β-actin internal control) in the DM group were higher than in the control group. Levels of P2X3 protein in T2DM rats treated with nano emodin were significantly lower than in the DM group. There were no differences in the levels of P2X3 protein when comparing DRG from the DM group and DM + nanocarrier group. Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group
    Recombinant Human Or Rat P2x3 Receptors, supplied by Pfizer Inc, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/recombinant human or rat p2x3 receptors/product/Pfizer Inc
    Average 90 stars, based on 1 article reviews
    recombinant human or rat p2x3 receptors - by Bioz Stars, 2026-06
    90/100 stars
    		  Buy from Supplier
    small molecule antagonist of human p2x3 receptors af-219  (Afferent Pharmaceuticals)
    90
    Afferent Pharmaceuticals small molecule antagonist of human p2x3 receptors af-219
    Effect of nano emodin on the expression of <t>P2X3</t> mRNA and protein in the DRG of T2DM rats. a. Expression of P2X3 mRNA was examined using real time RT-PCR. Expression levels of P2X3 mRNA in the T2DM group were higher than in the control group (p < 0.05, n = 8 for each group). Levels of P2X3 mRNA in T2DM rats treated with nano emodin were significantly lower than in the untreated T2DM group (p < 0.05, n = 8 for each group). There were no differences in expression levels of P2X3 mRNA when comparing the DRG from the DM group and DM + nanocarrier group (p > 0.05, n = 8 for each group). Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group. b. The expression of P2X3 protein in the DRG was examined using Western blots. Image analysis revealed that levels (assessed by integrated optical density) of P2X3 protein (normalized to each β-actin internal control) in the DM group were higher than in the control group. Levels of P2X3 protein in T2DM rats treated with nano emodin were significantly lower than in the DM group. There were no differences in the levels of P2X3 protein when comparing DRG from the DM group and DM + nanocarrier group. Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group
    Small Molecule Antagonist Of Human P2x3 Receptors Af 219, supplied by Afferent Pharmaceuticals, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/small molecule antagonist of human p2x3 receptors af-219/product/Afferent Pharmaceuticals
    Average 90 stars, based on 1 article reviews
    small molecule antagonist of human p2x3 receptors af-219 - by Bioz Stars, 2026-06
    90/100 stars
    		  Buy from Supplier

    Image Search Results


    (A, B) Overall structure (A) and cryo-EM density map (B) of the sivopixant- and ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In A, the sivopixant and ATP molecules are shown in sphere representation. In B, the ligand densities are shown in gray. (C) The dolphin-shaped P2X3 subunit is colored differently according to each structural feature. The cryo-EM densities for sivopixant and ATP are shown. (D) Structure of the sivopixant- and ATP-bound human P2X3 receptor viewed perpendicular to the membrane from the extracellular side. (E) The transmembrane domain structures of the sivopixant- and ATP-bound P2X3 structure (left panel, this study) and the apo P2X3 structure (right panel, PDB ID: 5SVJ) viewed from the extracellular side. (F, G) The overall structure (F) and cryo-EM density map (G) of the ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In F, ATP molecules are shown in sphere representation, and the cryo-EM density for ATP is also shown. In G, ATP densities are shown in gray. (H) The transmembrane domain structures of the ATP-bound P2X3 structure (this study, left panel), the desensitized P2X3 structure (middle panel, PDB ID: 5SVL), and the open P2X3 structure (right panel, PDB ID: 5SVK) viewed from the extracellular side.

    Journal: bioRxiv

    Article Title: Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

    doi: 10.64898/2026.01.03.697462

    Figure Lengend Snippet: (A, B) Overall structure (A) and cryo-EM density map (B) of the sivopixant- and ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In A, the sivopixant and ATP molecules are shown in sphere representation. In B, the ligand densities are shown in gray. (C) The dolphin-shaped P2X3 subunit is colored differently according to each structural feature. The cryo-EM densities for sivopixant and ATP are shown. (D) Structure of the sivopixant- and ATP-bound human P2X3 receptor viewed perpendicular to the membrane from the extracellular side. (E) The transmembrane domain structures of the sivopixant- and ATP-bound P2X3 structure (left panel, this study) and the apo P2X3 structure (right panel, PDB ID: 5SVJ) viewed from the extracellular side. (F, G) The overall structure (F) and cryo-EM density map (G) of the ATP-bound human P2X3 receptor viewed parallel to the membrane. Each subunit is colored distinctly. In F, ATP molecules are shown in sphere representation, and the cryo-EM density for ATP is also shown. In G, ATP densities are shown in gray. (H) The transmembrane domain structures of the ATP-bound P2X3 structure (this study, left panel), the desensitized P2X3 structure (middle panel, PDB ID: 5SVL), and the open P2X3 structure (right panel, PDB ID: 5SVK) viewed from the extracellular side.

    Article Snippet: The DNA sequence encoding the functional construct of human P2X3 for the structural studies ( ) was synthesized by Genewiz Inc. (Suzhou, China) and subcloned into a pFastBac vector containing a Twin-Strep tag, an EGFP tag, and a Tobacco etch virus (TEV) protease cleavage site at the N-terminus.

    Techniques: Cryo-EM Sample Prep, Membrane

    (A) Overall structure of the sivopixant- and ATP-bound human P2X3 receptor (upper-left panel) and a close-up view of the sivopixant binding site (lower-left panel) viewed perpendicular to the membrane from the extracellular side. Close-up views of the sivopixant binding site are shown from two different angles (upper-right and lower-right panels). The ligand molecules and amino acid residues involved in sivopixant binding are shown in stick representation. Dotted lines represent hydrogen bonds. (B) Schematic diagram of the interactions between P2X3 and sivopixant. Dotted lines represent hydrogen bonds. (C) Amino acid sequence alignment of P2X3 receptors from Mus musculus (Q3UR32.1), Rattus norvegicus (P49654.1), Canis familiaris (XP_038280235.1), Bos taurus (XP_059731161.1), Gallus gallus (NP_001384137.1), and Danio rerio (NP_571698.3); P2X receptors from Homo sapiens (P2X1: P51575.1; P2X2: Q9UBL9.1; P2X3: P56373.2; P2X4: Q99571.2; P2X5: Q93086.4; P2X6: O15547.2; and P2X7: Q99572.4) as well as the Mus musculus P2X2 receptor (Q8K3P1.2) and Rattus norvegicus P2X2 receptor (CAA71046.1). The residues involved in sivopixant binding are shown. The blue circles indicate the residues shown in B.

    Journal: bioRxiv

    Article Title: Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

    doi: 10.64898/2026.01.03.697462

    Figure Lengend Snippet: (A) Overall structure of the sivopixant- and ATP-bound human P2X3 receptor (upper-left panel) and a close-up view of the sivopixant binding site (lower-left panel) viewed perpendicular to the membrane from the extracellular side. Close-up views of the sivopixant binding site are shown from two different angles (upper-right and lower-right panels). The ligand molecules and amino acid residues involved in sivopixant binding are shown in stick representation. Dotted lines represent hydrogen bonds. (B) Schematic diagram of the interactions between P2X3 and sivopixant. Dotted lines represent hydrogen bonds. (C) Amino acid sequence alignment of P2X3 receptors from Mus musculus (Q3UR32.1), Rattus norvegicus (P49654.1), Canis familiaris (XP_038280235.1), Bos taurus (XP_059731161.1), Gallus gallus (NP_001384137.1), and Danio rerio (NP_571698.3); P2X receptors from Homo sapiens (P2X1: P51575.1; P2X2: Q9UBL9.1; P2X3: P56373.2; P2X4: Q99571.2; P2X5: Q93086.4; P2X6: O15547.2; and P2X7: Q99572.4) as well as the Mus musculus P2X2 receptor (Q8K3P1.2) and Rattus norvegicus P2X2 receptor (CAA71046.1). The residues involved in sivopixant binding are shown. The blue circles indicate the residues shown in B.

    Article Snippet: The DNA sequence encoding the functional construct of human P2X3 for the structural studies ( ) was synthesized by Genewiz Inc. (Suzhou, China) and subcloned into a pFastBac vector containing a Twin-Strep tag, an EGFP tag, and a Tobacco etch virus (TEV) protease cleavage site at the N-terminus.

    Techniques: Binding Assay, Membrane, Sequencing

    (A) Representative current traces of the effects of sivopixant on human P2X3 currents at different ATP concentrations. (B) Effects of sivopixant on ATP (0.1, 1 and 10 µM)-evoked currents of human P2X3 (mean ± SEM, n = 3-4). (C, E) Representative current traces of sivopixant effects at 1 μM (C) and 0.3 μM (E) on ATP-evoked currents of human P2X3 and its mutants (C: M96W, M165W, and Y285W; E: T82I). (D, F) Effects of 1 μM (D) and 0.3 μM (F) sivopixant on the ATP-evoked currents of human P2X3 and its mutants (mean ± SEM, n = 3-5). Two-way ANOVA followed by Tukey‘s multiple comparisons test (B) and one-side one-way ANOVA followed by post hoc test (D, F), **p < 0.01, ****p < 0.0001 vs. WT). The hP2X3 WT data shown in and were obtained from the same cells and are shown in the respective panels for comparison.

    Journal: bioRxiv

    Article Title: Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

    doi: 10.64898/2026.01.03.697462

    Figure Lengend Snippet: (A) Representative current traces of the effects of sivopixant on human P2X3 currents at different ATP concentrations. (B) Effects of sivopixant on ATP (0.1, 1 and 10 µM)-evoked currents of human P2X3 (mean ± SEM, n = 3-4). (C, E) Representative current traces of sivopixant effects at 1 μM (C) and 0.3 μM (E) on ATP-evoked currents of human P2X3 and its mutants (C: M96W, M165W, and Y285W; E: T82I). (D, F) Effects of 1 μM (D) and 0.3 μM (F) sivopixant on the ATP-evoked currents of human P2X3 and its mutants (mean ± SEM, n = 3-5). Two-way ANOVA followed by Tukey‘s multiple comparisons test (B) and one-side one-way ANOVA followed by post hoc test (D, F), **p < 0.01, ****p < 0.0001 vs. WT). The hP2X3 WT data shown in and were obtained from the same cells and are shown in the respective panels for comparison.

    Article Snippet: The DNA sequence encoding the functional construct of human P2X3 for the structural studies ( ) was synthesized by Genewiz Inc. (Suzhou, China) and subcloned into a pFastBac vector containing a Twin-Strep tag, an EGFP tag, and a Tobacco etch virus (TEV) protease cleavage site at the N-terminus.

    Techniques: Comparison

    (A-F) Close-up views of the sivopixant binding site of the sivopixant- and ATP-bound P2X3 structure (in this study, yellow and blue). The human P2X1 structure (PDB ID: 9C2A) (A), the human P2X2 structure (PDB ID: 9DDV) (B), the human P2X4 structure (PDB ID: 9BQH) (C), the human P2X7 structure (PDB ID: 9E3M) (D), and the predicted heterotrimer structure formed by two P2X2 subunits and one P2X3 subunit (AlphaFold3, ipTM=0.71) (E, F) are superposed onto the P2X3 structure and shown in gray. In E, the gray chain superposed onto the yellow chain is the P2X2 subunit, while the gray chain superposed onto the blue chain is the P2X3 subunit. In F, the gray chain superposed onto the yellow chain is the P2X3 subunit, while the gray chain superposed onto the blue chain is the P2X2 subunit.

    Journal: bioRxiv

    Article Title: Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

    doi: 10.64898/2026.01.03.697462

    Figure Lengend Snippet: (A-F) Close-up views of the sivopixant binding site of the sivopixant- and ATP-bound P2X3 structure (in this study, yellow and blue). The human P2X1 structure (PDB ID: 9C2A) (A), the human P2X2 structure (PDB ID: 9DDV) (B), the human P2X4 structure (PDB ID: 9BQH) (C), the human P2X7 structure (PDB ID: 9E3M) (D), and the predicted heterotrimer structure formed by two P2X2 subunits and one P2X3 subunit (AlphaFold3, ipTM=0.71) (E, F) are superposed onto the P2X3 structure and shown in gray. In E, the gray chain superposed onto the yellow chain is the P2X2 subunit, while the gray chain superposed onto the blue chain is the P2X3 subunit. In F, the gray chain superposed onto the yellow chain is the P2X3 subunit, while the gray chain superposed onto the blue chain is the P2X2 subunit.

    Article Snippet: The DNA sequence encoding the functional construct of human P2X3 for the structural studies ( ) was synthesized by Genewiz Inc. (Suzhou, China) and subcloned into a pFastBac vector containing a Twin-Strep tag, an EGFP tag, and a Tobacco etch virus (TEV) protease cleavage site at the N-terminus.

    Techniques: Binding Assay

    (A) Representative current traces of the effects of sivopixant on ATP-evoked currents of human P2X3 wild type (WT) and its gain-of-function mutant (GOF). (B) Effects of sivopixant on ATP-evoked currents of human P2X3 and its mutant (mean ± SEM, n = 3-4). (One-way ANOVA followed by Tukey‘s multiple comparisons test, ***p < 0.001 hP2X1GOF vs. hP2X1-WT, ****p < 0.0001 hP2X2GOF vs. hP2X2-WT). The hP2X3 WT data shown in and were obtained from the same cells and are shown in the respective panels for comparison.

    Journal: bioRxiv

    Article Title: Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

    doi: 10.64898/2026.01.03.697462

    Figure Lengend Snippet: (A) Representative current traces of the effects of sivopixant on ATP-evoked currents of human P2X3 wild type (WT) and its gain-of-function mutant (GOF). (B) Effects of sivopixant on ATP-evoked currents of human P2X3 and its mutant (mean ± SEM, n = 3-4). (One-way ANOVA followed by Tukey‘s multiple comparisons test, ***p < 0.001 hP2X1GOF vs. hP2X1-WT, ****p < 0.0001 hP2X2GOF vs. hP2X2-WT). The hP2X3 WT data shown in and were obtained from the same cells and are shown in the respective panels for comparison.

    Article Snippet: The DNA sequence encoding the functional construct of human P2X3 for the structural studies ( ) was synthesized by Genewiz Inc. (Suzhou, China) and subcloned into a pFastBac vector containing a Twin-Strep tag, an EGFP tag, and a Tobacco etch virus (TEV) protease cleavage site at the N-terminus.

    Techniques: Mutagenesis, Comparison

    (A) Superimposition of the sivopixant- and ATP-bound P2X3 structure (in this study, blue) and the ATP-bound, open P2X3 structure (PDB ID: 5SVK, red) onto the apo, closed P2X3 structure (PDB ID: 5SVJ, gray) viewed parallel to the membrane. Close-up views of the dorsal fin, left flipper, and lower body domains are also shown. The arrows indicate conformational changes in the open P2X3 structure (red) and the sivopixant- and ATP-bound P2X3 structure (blue). (B, C) Close-up view of the ATP binding site of the sivopixant- and ATP-bound P2X3 structure (in this study, blue) (B) and the open P2X3 structure (PDB ID: 5SVK, red) (C). The ATP molecules and amino acid residues involved in ATP binding are shown in stick representation. Dotted lines represent hydrogen bonds. (D, E) Superimposition of the open P2X3 structure (PDB ID: 5SVK, red) (D) and the sivopixant- and ATP-bound P2X3 structure (this study, blue) (E) onto the apo P2X3 structure (PDB ID: 5SVJ, gray). Only the transmembrane and body domains from the two subunits in the foreground are shown.

    Journal: bioRxiv

    Article Title: Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

    doi: 10.64898/2026.01.03.697462

    Figure Lengend Snippet: (A) Superimposition of the sivopixant- and ATP-bound P2X3 structure (in this study, blue) and the ATP-bound, open P2X3 structure (PDB ID: 5SVK, red) onto the apo, closed P2X3 structure (PDB ID: 5SVJ, gray) viewed parallel to the membrane. Close-up views of the dorsal fin, left flipper, and lower body domains are also shown. The arrows indicate conformational changes in the open P2X3 structure (red) and the sivopixant- and ATP-bound P2X3 structure (blue). (B, C) Close-up view of the ATP binding site of the sivopixant- and ATP-bound P2X3 structure (in this study, blue) (B) and the open P2X3 structure (PDB ID: 5SVK, red) (C). The ATP molecules and amino acid residues involved in ATP binding are shown in stick representation. Dotted lines represent hydrogen bonds. (D, E) Superimposition of the open P2X3 structure (PDB ID: 5SVK, red) (D) and the sivopixant- and ATP-bound P2X3 structure (this study, blue) (E) onto the apo P2X3 structure (PDB ID: 5SVJ, gray). Only the transmembrane and body domains from the two subunits in the foreground are shown.

    Article Snippet: The DNA sequence encoding the functional construct of human P2X3 for the structural studies ( ) was synthesized by Genewiz Inc. (Suzhou, China) and subcloned into a pFastBac vector containing a Twin-Strep tag, an EGFP tag, and a Tobacco etch virus (TEV) protease cleavage site at the N-terminus.

    Techniques: Membrane, Binding Assay

    (A) Close-up view of the sivopixant binding site of the P2X3 receptor. Superimposition of the sivopixant- and ATP-bound P2X3 structure (this study, blue) and the open P2X3 structure (PDB ID: 5SVK, red) onto the apo P2X3 structure (PDB ID: 5SVJ, gray) viewed perpendicular to the membrane from the extracellular side. Dotted lines indicate the distance (Å) between the Cα atoms of Glu289 in two adjacent subunits. (B-E) MD simulations using the sivopixant- and ATP-bound structure with both retained (B), ATP deleted (C), sivopixant deleted (D) and both deleted (E) as starting models. The distance plots of Cα atoms between Glu289 of two adjacent subunits are shown. The average distances in the trimer are shown.

    Journal: bioRxiv

    Article Title: Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

    doi: 10.64898/2026.01.03.697462

    Figure Lengend Snippet: (A) Close-up view of the sivopixant binding site of the P2X3 receptor. Superimposition of the sivopixant- and ATP-bound P2X3 structure (this study, blue) and the open P2X3 structure (PDB ID: 5SVK, red) onto the apo P2X3 structure (PDB ID: 5SVJ, gray) viewed perpendicular to the membrane from the extracellular side. Dotted lines indicate the distance (Å) between the Cα atoms of Glu289 in two adjacent subunits. (B-E) MD simulations using the sivopixant- and ATP-bound structure with both retained (B), ATP deleted (C), sivopixant deleted (D) and both deleted (E) as starting models. The distance plots of Cα atoms between Glu289 of two adjacent subunits are shown. The average distances in the trimer are shown.

    Article Snippet: The DNA sequence encoding the functional construct of human P2X3 for the structural studies ( ) was synthesized by Genewiz Inc. (Suzhou, China) and subcloned into a pFastBac vector containing a Twin-Strep tag, an EGFP tag, and a Tobacco etch virus (TEV) protease cleavage site at the N-terminus.

    Techniques: Binding Assay, Membrane

    Cartoon diagrams illustrating the conformational changes of P2X3 from the apo state (middle) to the ATP-bound, open state (left) and the sivopixant- and ATP-bound, closed state (right). The arrows indicate conformational changes between two states.

    Journal: bioRxiv

    Article Title: Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

    doi: 10.64898/2026.01.03.697462

    Figure Lengend Snippet: Cartoon diagrams illustrating the conformational changes of P2X3 from the apo state (middle) to the ATP-bound, open state (left) and the sivopixant- and ATP-bound, closed state (right). The arrows indicate conformational changes between two states.

    Article Snippet: The DNA sequence encoding the functional construct of human P2X3 for the structural studies ( ) was synthesized by Genewiz Inc. (Suzhou, China) and subcloned into a pFastBac vector containing a Twin-Strep tag, an EGFP tag, and a Tobacco etch virus (TEV) protease cleavage site at the N-terminus.

    Techniques:

    MK‐7264 antagonism of human P2X3 receptor is associated with an onset of slowed desensitisation. (a) Representative trace showing a diminished peak response and appearance of slow desensitisation are associated with MK‐7264 antagonism. (b) Representative superimposed trace showing time‐dependent recovery of P2X3 fast desensitisation following MK‐7264 (300 nM) wash‐off. Agonist applied every 4 min. (c) Relationship between MK‐7264 concentration and the rate of desensitisation. Time constants (τ values) were derived from single exponential curves fitted to the desensitisation phase 250–750 ms after the peak response. The τ values were compared with a Kruskal–Wallis ANOVA (P < .05) followed by Dunn's post hoc test; N = 6. (d) The change in shape of the current following MK‐7264 antagonism quantified as a fractional response (residual current, 1 s after onset of agonist response over peak current) and compared with a Kruskal–Wallis ANOVA followed by Dunn's post hoc test. *P < 0.05 versus control response; N = 7

    Journal: British Journal of Pharmacology

    Article Title: Action of MK‐7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation

    doi: 10.1111/bph.14677

    Figure Lengend Snippet: MK‐7264 antagonism of human P2X3 receptor is associated with an onset of slowed desensitisation. (a) Representative trace showing a diminished peak response and appearance of slow desensitisation are associated with MK‐7264 antagonism. (b) Representative superimposed trace showing time‐dependent recovery of P2X3 fast desensitisation following MK‐7264 (300 nM) wash‐off. Agonist applied every 4 min. (c) Relationship between MK‐7264 concentration and the rate of desensitisation. Time constants (τ values) were derived from single exponential curves fitted to the desensitisation phase 250–750 ms after the peak response. The τ values were compared with a Kruskal–Wallis ANOVA (P < .05) followed by Dunn's post hoc test; N = 6. (d) The change in shape of the current following MK‐7264 antagonism quantified as a fractional response (residual current, 1 s after onset of agonist response over peak current) and compared with a Kruskal–Wallis ANOVA followed by Dunn's post hoc test. *P < 0.05 versus control response; N = 7

    Article Snippet: Cells 1321N1 astrocytoma lines (RRID:CVCL_0110) stably transfected with human P2X2, P2X3, or co‐expressing P2X2 and P2X3 receptors were used in all experiments and provided by Afferent Pharmaceuticals Ltd.

    Techniques: Concentration Assay, Derivative Assay, Control

    MK‐7264 activity at human P2X2, P2X3, and P2X2/3 receptors. (a–c) Representative concatenated traces of whole‐cell patch‐clamp recordings for human P2X3 (a), P2X2/3 (b), and P2X2 (c) receptor currents in 1312N1 stably transfected cells. Fully recovered P2X3 currents were evoked by 10‐μM α,β‐meATP applied for 1 s every 4 min and 10‐μM α,β‐meATP applied for 2 s at 30‐s intervals for P2X2/3 currents. P2X2 currents were evoked by 10‐μM ATP every 4 min. MK‐7264 was applied 4 min, 30 s, and 4 min prior to agonist application for P2X3 (1 μM), P2X2/3 (1 μM), and P2X2 (10 μM) receptors, respectively. Agonist application is indicated by the perfusion bar. Currents shaded in grey are in the presence of MK‐7264. (d) MK‐7264 concentration–dependent inhibition curve at human P2X3 (closed circles) and P2X2/3 receptors (open circles; N = 5). Data sets were compared with an F test and found to be significantly different from one another (F = 11.74, P = .018). (e) Effect of MK‐7264 on α,β‐meATP concentration–response curve at P2X3 receptors. Currents are in the presence of 300‐nM MK‐7264 (open circles) or vehicle control (closed circles; N = 6). MK‐7264 was applied for 4 min prior to agonist application. EC50 values were compared with a paired sample t test and found to be significantly different (P = .018). The holding potential was −80 mV for all experiments

    Journal: British Journal of Pharmacology

    Article Title: Action of MK‐7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation

    doi: 10.1111/bph.14677

    Figure Lengend Snippet: MK‐7264 activity at human P2X2, P2X3, and P2X2/3 receptors. (a–c) Representative concatenated traces of whole‐cell patch‐clamp recordings for human P2X3 (a), P2X2/3 (b), and P2X2 (c) receptor currents in 1312N1 stably transfected cells. Fully recovered P2X3 currents were evoked by 10‐μM α,β‐meATP applied for 1 s every 4 min and 10‐μM α,β‐meATP applied for 2 s at 30‐s intervals for P2X2/3 currents. P2X2 currents were evoked by 10‐μM ATP every 4 min. MK‐7264 was applied 4 min, 30 s, and 4 min prior to agonist application for P2X3 (1 μM), P2X2/3 (1 μM), and P2X2 (10 μM) receptors, respectively. Agonist application is indicated by the perfusion bar. Currents shaded in grey are in the presence of MK‐7264. (d) MK‐7264 concentration–dependent inhibition curve at human P2X3 (closed circles) and P2X2/3 receptors (open circles; N = 5). Data sets were compared with an F test and found to be significantly different from one another (F = 11.74, P = .018). (e) Effect of MK‐7264 on α,β‐meATP concentration–response curve at P2X3 receptors. Currents are in the presence of 300‐nM MK‐7264 (open circles) or vehicle control (closed circles; N = 6). MK‐7264 was applied for 4 min prior to agonist application. EC50 values were compared with a paired sample t test and found to be significantly different (P = .018). The holding potential was −80 mV for all experiments

    Article Snippet: Cells 1321N1 astrocytoma lines (RRID:CVCL_0110) stably transfected with human P2X2, P2X3, or co‐expressing P2X2 and P2X3 receptors were used in all experiments and provided by Afferent Pharmaceuticals Ltd.

    Techniques: Activity Assay, Patch Clamp, Stable Transfection, Transfection, Concentration Assay, Inhibition, Control

    MK‐7264 antagonism of human P2X3 receptor is associated with an onset of slowed desensitisation. (a) Representative trace showing a diminished peak response and appearance of slow desensitisation are associated with MK‐7264 antagonism. (b) Representative superimposed trace showing time‐dependent recovery of P2X3 fast desensitisation following MK‐7264 (300 nM) wash‐off. Agonist applied every 4 min. (c) Relationship between MK‐7264 concentration and the rate of desensitisation. Time constants (τ values) were derived from single exponential curves fitted to the desensitisation phase 250–750 ms after the peak response. The τ values were compared with a Kruskal–Wallis ANOVA (P < .05) followed by Dunn's post hoc test; N = 6. (d) The change in shape of the current following MK‐7264 antagonism quantified as a fractional response (residual current, 1 s after onset of agonist response over peak current) and compared with a Kruskal–Wallis ANOVA followed by Dunn's post hoc test. *P < 0.05 versus control response; N = 7

    Journal: British Journal of Pharmacology

    Article Title: Action of MK‐7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation

    doi: 10.1111/bph.14677

    Figure Lengend Snippet: MK‐7264 antagonism of human P2X3 receptor is associated with an onset of slowed desensitisation. (a) Representative trace showing a diminished peak response and appearance of slow desensitisation are associated with MK‐7264 antagonism. (b) Representative superimposed trace showing time‐dependent recovery of P2X3 fast desensitisation following MK‐7264 (300 nM) wash‐off. Agonist applied every 4 min. (c) Relationship between MK‐7264 concentration and the rate of desensitisation. Time constants (τ values) were derived from single exponential curves fitted to the desensitisation phase 250–750 ms after the peak response. The τ values were compared with a Kruskal–Wallis ANOVA (P < .05) followed by Dunn's post hoc test; N = 6. (d) The change in shape of the current following MK‐7264 antagonism quantified as a fractional response (residual current, 1 s after onset of agonist response over peak current) and compared with a Kruskal–Wallis ANOVA followed by Dunn's post hoc test. *P < 0.05 versus control response; N = 7

    Article Snippet: 1321N1 astrocytoma lines (RRID:CVCL_0110) stably transfected with human P2X2, P2X3, or co‐expressing P2X2 and P2X3 receptors were used in all experiments and provided by Afferent Pharmaceuticals Ltd.

    Techniques: Concentration Assay, Derivative Assay, Control

    MK‐7264 activity at human P2X2, P2X3, and P2X2/3 receptors. (a–c) Representative concatenated traces of whole‐cell patch‐clamp recordings for human P2X3 (a), P2X2/3 (b), and P2X2 (c) receptor currents in 1312N1 stably transfected cells. Fully recovered P2X3 currents were evoked by 10‐μM α,β‐meATP applied for 1 s every 4 min and 10‐μM α,β‐meATP applied for 2 s at 30‐s intervals for P2X2/3 currents. P2X2 currents were evoked by 10‐μM ATP every 4 min. MK‐7264 was applied 4 min, 30 s, and 4 min prior to agonist application for P2X3 (1 μM), P2X2/3 (1 μM), and P2X2 (10 μM) receptors, respectively. Agonist application is indicated by the perfusion bar. Currents shaded in grey are in the presence of MK‐7264. (d) MK‐7264 concentration–dependent inhibition curve at human P2X3 (closed circles) and P2X2/3 receptors (open circles; N = 5). Data sets were compared with an F test and found to be significantly different from one another (F = 11.74, P = .018). (e) Effect of MK‐7264 on α,β‐meATP concentration–response curve at P2X3 receptors. Currents are in the presence of 300‐nM MK‐7264 (open circles) or vehicle control (closed circles; N = 6). MK‐7264 was applied for 4 min prior to agonist application. EC50 values were compared with a paired sample t test and found to be significantly different (P = .018). The holding potential was −80 mV for all experiments

    Journal: British Journal of Pharmacology

    Article Title: Action of MK‐7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation

    doi: 10.1111/bph.14677

    Figure Lengend Snippet: MK‐7264 activity at human P2X2, P2X3, and P2X2/3 receptors. (a–c) Representative concatenated traces of whole‐cell patch‐clamp recordings for human P2X3 (a), P2X2/3 (b), and P2X2 (c) receptor currents in 1312N1 stably transfected cells. Fully recovered P2X3 currents were evoked by 10‐μM α,β‐meATP applied for 1 s every 4 min and 10‐μM α,β‐meATP applied for 2 s at 30‐s intervals for P2X2/3 currents. P2X2 currents were evoked by 10‐μM ATP every 4 min. MK‐7264 was applied 4 min, 30 s, and 4 min prior to agonist application for P2X3 (1 μM), P2X2/3 (1 μM), and P2X2 (10 μM) receptors, respectively. Agonist application is indicated by the perfusion bar. Currents shaded in grey are in the presence of MK‐7264. (d) MK‐7264 concentration–dependent inhibition curve at human P2X3 (closed circles) and P2X2/3 receptors (open circles; N = 5). Data sets were compared with an F test and found to be significantly different from one another (F = 11.74, P = .018). (e) Effect of MK‐7264 on α,β‐meATP concentration–response curve at P2X3 receptors. Currents are in the presence of 300‐nM MK‐7264 (open circles) or vehicle control (closed circles; N = 6). MK‐7264 was applied for 4 min prior to agonist application. EC50 values were compared with a paired sample t test and found to be significantly different (P = .018). The holding potential was −80 mV for all experiments

    Article Snippet: 1321N1 astrocytoma lines (RRID:CVCL_0110) stably transfected with human P2X2, P2X3, or co‐expressing P2X2 and P2X3 receptors were used in all experiments and provided by Afferent Pharmaceuticals Ltd.

    Techniques: Activity Assay, Patch Clamp, Stable Transfection, Transfection, Concentration Assay, Inhibition, Control

    Effect of nano emodin on the expression of P2X3 mRNA and protein in the DRG of T2DM rats. a. Expression of P2X3 mRNA was examined using real time RT-PCR. Expression levels of P2X3 mRNA in the T2DM group were higher than in the control group (p < 0.05, n = 8 for each group). Levels of P2X3 mRNA in T2DM rats treated with nano emodin were significantly lower than in the untreated T2DM group (p < 0.05, n = 8 for each group). There were no differences in expression levels of P2X3 mRNA when comparing the DRG from the DM group and DM + nanocarrier group (p > 0.05, n = 8 for each group). Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group. b. The expression of P2X3 protein in the DRG was examined using Western blots. Image analysis revealed that levels (assessed by integrated optical density) of P2X3 protein (normalized to each β-actin internal control) in the DM group were higher than in the control group. Levels of P2X3 protein in T2DM rats treated with nano emodin were significantly lower than in the DM group. There were no differences in the levels of P2X3 protein when comparing DRG from the DM group and DM + nanocarrier group. Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group

    Journal: Purinergic Signalling

    Article Title: Nanoparticle-encapsulated emodin decreases diabetic neuropathic pain probably via a mechanism involving P2X3 receptor in the dorsal root ganglia

    doi: 10.1007/s11302-017-9583-2

    Figure Lengend Snippet: Effect of nano emodin on the expression of P2X3 mRNA and protein in the DRG of T2DM rats. a. Expression of P2X3 mRNA was examined using real time RT-PCR. Expression levels of P2X3 mRNA in the T2DM group were higher than in the control group (p < 0.05, n = 8 for each group). Levels of P2X3 mRNA in T2DM rats treated with nano emodin were significantly lower than in the untreated T2DM group (p < 0.05, n = 8 for each group). There were no differences in expression levels of P2X3 mRNA when comparing the DRG from the DM group and DM + nanocarrier group (p > 0.05, n = 8 for each group). Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group. b. The expression of P2X3 protein in the DRG was examined using Western blots. Image analysis revealed that levels (assessed by integrated optical density) of P2X3 protein (normalized to each β-actin internal control) in the DM group were higher than in the control group. Levels of P2X3 protein in T2DM rats treated with nano emodin were significantly lower than in the DM group. There were no differences in the levels of P2X3 protein when comparing DRG from the DM group and DM + nanocarrier group. Results are expressed as mean ± SEM, n = 10. **p < 0.01 compared to the control group; ## p < 0.01 compared to the DM group

    Article Snippet: Cells were transiently transfected with the human pcDNA3.0-EGFP-P2X3 plasmid using Lipofectamine 2000 reagent (Invitrogen) according to the manufacturer’s instructions.

    Techniques: Expressing, Quantitative RT-PCR, Western Blot