a 3 ar antagonists  (Chembridge)

Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: Effect of ring substitution at the p-position on the binding affinity of anilides of the xanthine carboxylic congener (XCC) as adenosine receptor antagonists. The p-cyano analog is MRS 1754 [Kim et al., 2000b]. Ki values at the following human ARs are shown: A1(■), A2A (✦), A2B (●), and A3 (▲).

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques: Binding Assay

Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: Use of 1,4-dihydropyridines as a molecular template for antagonists of the human A3AR. Representative members of a library of DHP derivatives and their affinity (Ki in μM) in binding to the human A3AR are shown [Jiang et al., 1998].

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques: Binding Assay

Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: Use of 3,5-diacylpyridine derivatives, prepared by oxidation of the corresponding DHPs, as a molecular template for antagonists of the human A3AR. Representative members of a library of such pyridine derivatives and their affinity (Ki in μM) in binding to the human A3AR are shown [Li et al., 1999].

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques: Binding Assay

Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: A prodrug scheme for the oxidative generation of pyridinium salts which act as antagonists of the human A3AR from the corresponding 1-alkyldihydropyridine derivatives. Such antagonists are highly water-soluble in contrast to most other classes of A3AR antagonists, which are hydrophobic [Xie et al., 1999].

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques:

Journal: Drug development research

Article Title: Probing Adenosine and P2 Receptors: Design of Novel Purines and Nonpurines as Selective Ligands

doi: 10.1002/ddr.1113

Figure Lengend Snippet: Structural modifications of the adenosine moiety of P2Y1 receptor antagonists [Nandanan et al., 1999, 2000; Kim et al., 2000a]. The endogenous agonists of P2 receptors are nucleotides; however, bisphosphate analogs which act as antagonists have been identified. IC50 values at the turkey erythrocyte P2Y1 receptor for antagonism of phospholipase C activation by 30 nM 2-methylthio-adenosine 5′-diphosphate are indicated.

Article Snippet: In collaboration with Dr. Thomas Webb of ChemBridge Corp., we set out to use information derived from known A 3 AR antagonists to identify new leads for this receptor family and to explore both the pharmacophore relationships within the receptor family and the utility of pharmacophore database queries for the discovery of new leads [ Webb et al., 2000 ].

Techniques: Activation Assay

Journal: Journal of Immunology Research

Article Title: Inhibition of IL-17 and IL-23 in Human Keratinocytes by the A 3 Adenosine Receptor Agonist Piclidenoson

doi: 10.1155/2018/2310970

Figure Lengend Snippet: Piclidenoson inhibits the proliferation of HaCat cells. Proliferation assay was performed on HaCat cells that were incubated in the presence of piclidenoson (10 nM) and A 3 AR antagonist MRS 1523 (50 nM) for 48 hours ( ∗ p < 0.05).

Article Snippet: The A 3 AR antagonist MRS 1523 was purchased from Sigma (St. Louis, MO, USA) and diluted in the same manner as for piclidenoson.

Techniques: Proliferation Assay, Incubation

Journal: Journal of Immunology Research

Article Title: Inhibition of IL-17 and IL-23 in Human Keratinocytes by the A 3 Adenosine Receptor Agonist Piclidenoson

doi: 10.1155/2018/2310970

Figure Lengend Snippet: Piclidenoson downregulates A 3 AR protein expression level. HaCat cells were incubated in the presence and absence of piclidenoson and MRS 1523 for 48 hours. Downregulation of A 3 AR was demonstrated upon piclidenoson treatment and reversed by the introduction of MRS 1523 to the culture.

Article Snippet: The A 3 AR antagonist MRS 1523 was purchased from Sigma (St. Louis, MO, USA) and diluted in the same manner as for piclidenoson.

Techniques: Expressing, Incubation

Journal: Journal of Immunology Research

Article Title: Inhibition of IL-17 and IL-23 in Human Keratinocytes by the A 3 Adenosine Receptor Agonist Piclidenoson

doi: 10.1155/2018/2310970

Figure Lengend Snippet: Piclidenoson downregulates IL-17 and IL-23. HaCat cells were incubated in the presence and absence of piclidenoson (10 nM) and MRS 1523 (50 nM) for 48 hours. The expression level of the inflammatory cytokines IL-17 and IL-23 was tested by Western blot analysis.

Article Snippet: The A 3 AR antagonist MRS 1523 was purchased from Sigma (St. Louis, MO, USA) and diluted in the same manner as for piclidenoson.

Techniques: Incubation, Expressing, Western Blot

Journal: Arthritis Research & Therapy

Article Title: Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A 3 adenosine receptor expression

doi: 10.1186/ar2078

Figure Lengend Snippet: Immunohistochemistry analysis of A 3 AR expression in paws from AIA rats. We conducted immunohistochemistry staining of paraffin-embedded sections of paw from MTX-treated, CF101-treated and MTX+CF101-treated AIA rats. MTX treatment induced receptor expression, and treatment with CF101 alone or in combination with MTX resulted in receptor downregulation. A 3 AR, A 3 adenosine receptor; AIA, adjuvant-induced arthritis; MTX, methotrexate.

Article Snippet: The A 3 AR antagonist MRS1523 was purchased from Sigma (St. Louis, MO, USA) and diluted in the same manner as for CF101.

Techniques: Immunohistochemistry, Expressing, Staining

Journal: Arthritis Research & Therapy

Article Title: Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A 3 adenosine receptor expression

doi: 10.1186/ar2078

Figure Lengend Snippet: Ex vivo analysis of A 3 AR expression level in paw and PBMCs from AIA rats. (a, b) MTX treatment induced expression of A 3 AR mRNA and protein, and CF101 treatment resulted in receptor downregulation. (c) This was reflected in the PBMCs. (d) Expression of A 2A AR was also induced in paw extracts derived AIA rats treated with MTX. A 3 AR, A 3 adenosine receptor; AIA, adjuvant-induced arthritis; MTX, methotrexate; PBMC, peripheral blood mononuclear cell.

Article Snippet: The A 3 AR antagonist MRS1523 was purchased from Sigma (St. Louis, MO, USA) and diluted in the same manner as for CF101.

Techniques: Ex Vivo, Expressing, Derivative Assay

Journal: Arthritis Research & Therapy

Article Title: Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A 3 adenosine receptor expression

doi: 10.1186/ar2078

Figure Lengend Snippet: Effect of dipyridamole on the expression of A 3 AR in PBMCs from naïve rats. Dipyridamole (5 mg/kg intraperitoneally) was administered once to naïve rats and blood samples were drawn 2, 6, 24 and 48 hours after dipyridamole administration. Dipyridamole induced A 3 AR upregulation in PBMCs derived from treated rats. A 3 AR, A 3 adenosine receptor; PBMC, peripheral blood mononuclear cell.

Article Snippet: The A 3 AR antagonist MRS1523 was purchased from Sigma (St. Louis, MO, USA) and diluted in the same manner as for CF101.

Techniques: Expressing, Derivative Assay

Journal: Arthritis Research & Therapy

Article Title: Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A 3 adenosine receptor expression

doi: 10.1186/ar2078

Figure Lengend Snippet: A 3 AR expression level in PBMCs from RA patients. (a) Newly MTX treated RA patients. Western blots of the four patients at baseline and 10 weeks after MTX treatment are presented. Representative Western blots are shown at the bottom. (b) RA patients undergoing chronic treatment with MTX. Results are expressed as means ± standard error for 30 patients. (c) Double-stained immunofluorecence analysis of PBMCs from RA patients. A 3 AR expression on the cell surface of the CD4 + T cells was found. (d) Incubation of PBMCs from MTX-treated RA patients for 1 hour in RPMI 1640 supplemented with 10% foetal bovine serum in the presence of with CF101 (10 nmol/l) resulted in decreased expression of A 3 AR. A 3 AR, A 3 adenosine receptor; AIA, adjuvant-induced arthritis; MTX, methotrexate; PBMC, peripheral blood mononuclear cell; RA, rheumatoid arthritis.

Article Snippet: The A 3 AR antagonist MRS1523 was purchased from Sigma (St. Louis, MO, USA) and diluted in the same manner as for CF101.

Techniques: Expressing, Western Blot, Staining, Incubation

Journal: Arthritis Research & Therapy

Article Title: Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A 3 adenosine receptor expression

doi: 10.1186/ar2078

Figure Lengend Snippet: Effect of MTX on A 3 AR expression level on PBMCs from healthy individuals. (a) PBMCs (2 × 10 6 cells/ml) from healthy individuals were incubated in RPMI 1640 supplemented with 10% foetal bovine serum and activated with PHA (5 μg/ml) for 24 hours. MTX (1 μmol/l) was added for an additional 27 hours and ADA (1 unit/ml) for the last 3 hours. A 3 AR expression level was induced by MTX treatment. The introduction of ADA to the culture system reverted this effect and induced downregulation of the receptor level. (b) PBMCs (2 × 10 6 cells/ml) were incubated for 27 hours with adenosine (25 μmol/l) and ADA (1 unit/ml) was added to the culture system for the last 3 hours. Adenosine induced upregulation of A 3 AR expression level whereas the addition of ADA decreased the receptor level. (c) PBMCs from healthy individuals were incubated with 10% foetal bovine serum and activated with PHA (5 μg/ml) for 24 hours. MTX (1 μmol/l) was added for an additional 27 hours and CF101 (10 nmol/l), in the presence or absence of MRS1523 (10 nmol/l), was introduced into the culture system for the last 3 hours. CF101 introduction to MTX-treated, PHA-activated PBMCs induced receptor downregulation, and the MRS1523 counteracted this effect. A 3 AR, A 3 adenosine receptor; ADA, adenosine deaminase; MTX, methotrexate; PBMC, peripheral blood mononuclear cell; PHA, phytohemagglutinin; RA, rheumatoid arthritis.

Article Snippet: The A 3 AR antagonist MRS1523 was purchased from Sigma (St. Louis, MO, USA) and diluted in the same manner as for CF101.

Techniques: Expressing, Incubation

Journal: Cell Metabolism

Article Title: Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

doi: 10.1016/j.cmet.2017.06.014

Figure Lengend Snippet: Effect of Central THs on Liver and BAT (A) Protein levels of the AMPK pathway in the liver, WAT, muscle, and BAT (n = 8–17 rats/group). (B and C) Oil Red O (20×; scale bar, 100 μm) staining analysis (B) and TG levels in the liver (n = 8–9 rats/group) (C). (D) [ 3 H]-acetate incorporation into TGs in the liver (n = 6–7 rats/group). (E) mRNA levels of BAT genes (n = 5–7 rats/group). (F) Protein levels of UCP1 in the BAT (n = 14 rats/group). (G) 18 F-FDG uptake analysis (n = 8 rats/group). (H) Lipid oxidation rate, oxygen consumption rate in the BAT, and oxygen consumption in BAT mitochondria (n = 6–7 rats/group). (I) Electron microscopy images (4,000×; scale bar, 10 μm) and quantification of lipid droplet (LD) and mitochondria number/area unit, size, and ultrastructure in the BAT (n = 4 rats/experimental group, 30 images/animal). (J) Cumulative EE, RQ, and LA (n = 5 rats/group). (K) c-FOS images (10×; scale bar, 50 μm) and staining analysis in the dorsal nucleus of the vagus (DMV) (n = 4 rats/group, 9–32 sections/animal) of rats ICV treated with vehicle or T3. (L) Protein levels of the AMPK pathway in the liver of sham or VGX rats ICV treated with vehicle or T3 (n = 11–14 rats/group). (M) Sympathetic nerve activity (SNA) in the BAT (n = 8–11 rats/group) of rats ICV treated with vehicle or T3. (N) Protein levels of the AMPK pathway in the BAT of rats ICV treated with vehicle or T3 and s.c. treated with SR59230A (n = 7 rats/group). ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001 versus vehicle ICV. #p < 0.05 T3 ICV vehicle s.c. versus T3 ICV SR59230A s.c. Data are expressed as mean ± SEM. The bands in gels from (A), (F), (L), and (N) have been spliced from the same original gels. CC, central canal; HN, hypoglossal nucleus; ND, non-detected; SUV, standardized uptake value. See also Figure S1 .

Article Snippet: The adrenergic receptor beta 3 (β3-AR) specific antagonist SR59230A ([3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol-oxalate]; 3 mg/Kg/day dissolved in saline:DMSO, 1:50 saline:DMSO; Tocris Bioscience; Bristol, UK) ( , ) was administrated subcutaneously (s.c.) and animals were treated during 2 days before the T3 injections for rats and 7 days for SF1-Cre AMPKα1 flox/flox mice.

Techniques: Staining, Electron Microscopy, Activity Assay

Journal: Cell Metabolism

Article Title: Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

doi: 10.1016/j.cmet.2017.06.014

Figure Lengend Snippet:

Article Snippet: The adrenergic receptor beta 3 (β3-AR) specific antagonist SR59230A ([3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol-oxalate]; 3 mg/Kg/day dissolved in saline:DMSO, 1:50 saline:DMSO; Tocris Bioscience; Bristol, UK) ( , ) was administrated subcutaneously (s.c.) and animals were treated during 2 days before the T3 injections for rats and 7 days for SF1-Cre AMPKα1 flox/flox mice.

Techniques: Virus, Recombinant, Electron Microscopy, Labeling, Protease Inhibitor, Enzyme-linked Immunosorbent Assay, In Situ Hybridization, Software, In Vivo Imaging, Imaging, Transmission Assay, Microscopy, Thin Layer Chromatography, Mass Spectrometry, Real-time Polymerase Chain Reaction, Membrane