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Effects of AT2R and Mas receptor antagonists on CO-induced ˙ OH production. <t>PD123319</t> (100 μM) and A779 (100 μM) were dissolved in the perfusing medium and administered throughout the experimental period. The inserted graph depicts basal ˙ OH production in terms of 2,3-DHBA formation. Each column or symbol with a vertical bar indicates the mean ± SEM. The horizontal bar indicates exposure to 3000 ppm CO for 40 min. *Significant difference (p < 0.05) from CO alone by one-way ANOVA followed by Dunnett’s test.
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(A-D) Distance mapping of AT1R conformations based on the four NNMF components: (A) Aclosed (NNMF I), (B) Aoccl1 (NNMF II), (C) Aoccl2 (NNMF III), and (D) Aopen (NNMF IV). Colored surfaces reflect spin densities based on major distance peaks selected from the NNMF distributions. A representative frame from molecular dynamics simulations of <t>ZD7155-bound</t> AT1R is overlaid in gray. Colored arrows represent changes in label positions relative to the Aclosed map (light gray surfaces in (B), (C), and (D)).
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(A-D) Distance mapping of AT1R conformations based on the four NNMF components: (A) Aclosed (NNMF I), (B) Aoccl1 (NNMF II), (C) Aoccl2 (NNMF III), and (D) Aopen (NNMF IV). Colored surfaces reflect spin densities based on major distance peaks selected from the NNMF distributions. A representative frame from molecular dynamics simulations of <t>ZD7155-bound</t> AT1R is overlaid in gray. Colored arrows represent changes in label positions relative to the Aclosed map (light gray surfaces in (B), (C), and (D)).
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(A-D) Distance mapping of AT1R conformations based on the four NNMF components: (A) Aclosed (NNMF I), (B) Aoccl1 (NNMF II), (C) Aoccl2 (NNMF III), and (D) Aopen (NNMF IV). Colored surfaces reflect spin densities based on major distance peaks selected from the NNMF distributions. A representative frame from molecular dynamics simulations of <t>ZD7155-bound</t> AT1R is overlaid in gray. Colored arrows represent changes in label positions relative to the Aclosed map (light gray surfaces in (B), (C), and (D)).
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Effects of AT2R and Mas receptor antagonists on CO-induced ˙ OH production. PD123319 (100 μM) and A779 (100 μM) were dissolved in the perfusing medium and administered throughout the experimental period. The inserted graph depicts basal ˙ OH production in terms of 2,3-DHBA formation. Each column or symbol with a vertical bar indicates the mean ± SEM. The horizontal bar indicates exposure to 3000 ppm CO for 40 min. *Significant difference (p < 0.05) from CO alone by one-way ANOVA followed by Dunnett’s test.

Journal: Scientific Reports

Article Title: Blockade of the renin-angiotensin system suppresses hydroxyl radical production in the rat striatum during carbon monoxide poisoning

doi: 10.1038/s41598-020-59377-6

Figure Lengend Snippet: Effects of AT2R and Mas receptor antagonists on CO-induced ˙ OH production. PD123319 (100 μM) and A779 (100 μM) were dissolved in the perfusing medium and administered throughout the experimental period. The inserted graph depicts basal ˙ OH production in terms of 2,3-DHBA formation. Each column or symbol with a vertical bar indicates the mean ± SEM. The horizontal bar indicates exposure to 3000 ppm CO for 40 min. *Significant difference (p < 0.05) from CO alone by one-way ANOVA followed by Dunnett’s test.

Article Snippet: PD123319, ZD7155, A779, SR202 and EHT1864 were purchased from Tocris Bioscience (Bristol, UK).

Techniques:

˙ OH production by intrastriatal administration of AngII (top) and the effects of AT1R and AT2R antagonists (middle) and NOX and Rac inhibitors (bottom) on AngII-induced ˙ OH production. AngII (100 nmol/2 μL or 200 nmol/2 μL) was dissolve in sterilized saline and administered into the striatum at 0.1 μL/min for 20 min. Losartan (1 mM), PD123319 (100 μM), DPI (100 μM), AEBSF (100 μM) and EFT1864 (100 μM) were dissolved in the perfusing medium and administered throughout the experimental period. The inserted graphs depict basal ˙ OH production in terms of 2,3-DHBA formation. Each column or symbol with a vertical bar indicates the mean ± SEM. The horizontal bars indicate administration of AngII. *Significant difference (p < 0.05) from 0 nmol AngII (saline alone) (top) and “None” (neither antagonists nor inhibitors) or 100 nmol AngII alone (middle and bottom) by one-way ANOVA followed by Dunnett’s test.

Journal: Scientific Reports

Article Title: Blockade of the renin-angiotensin system suppresses hydroxyl radical production in the rat striatum during carbon monoxide poisoning

doi: 10.1038/s41598-020-59377-6

Figure Lengend Snippet: ˙ OH production by intrastriatal administration of AngII (top) and the effects of AT1R and AT2R antagonists (middle) and NOX and Rac inhibitors (bottom) on AngII-induced ˙ OH production. AngII (100 nmol/2 μL or 200 nmol/2 μL) was dissolve in sterilized saline and administered into the striatum at 0.1 μL/min for 20 min. Losartan (1 mM), PD123319 (100 μM), DPI (100 μM), AEBSF (100 μM) and EFT1864 (100 μM) were dissolved in the perfusing medium and administered throughout the experimental period. The inserted graphs depict basal ˙ OH production in terms of 2,3-DHBA formation. Each column or symbol with a vertical bar indicates the mean ± SEM. The horizontal bars indicate administration of AngII. *Significant difference (p < 0.05) from 0 nmol AngII (saline alone) (top) and “None” (neither antagonists nor inhibitors) or 100 nmol AngII alone (middle and bottom) by one-way ANOVA followed by Dunnett’s test.

Article Snippet: PD123319, ZD7155, A779, SR202 and EHT1864 were purchased from Tocris Bioscience (Bristol, UK).

Techniques: Saline

Effects of AT1R and AT2R antagonists on CO-induced cAMP production (left) and forskolin-ws-induced ˙ OH production (right). Losartan (50 μM) and PD123319 (100 μM) were dissolved in the perfusing medium and administered throughout the experimental period. Forskolin-ws (5 nmol/μL) was dissolve in sterilized saline and administered into the striatum at 0.1 µL/min for 10 min. The inserted graphs depict basal cAMP production (left) and basal ˙ OH production in terms of 2,3-DHBA formation (right). Each column or symbol with a vertical bar indicates the mean ± SEM. The horizontal bars indicate 40-min exposure to 3000 ppm CO (left) or administration of 5 nmol forskolin-ws (right). *Significant difference (p < 0.05) from “None” (no antagonists) by one-way ANOVA followed by Dunnett’s test.

Journal: Scientific Reports

Article Title: Blockade of the renin-angiotensin system suppresses hydroxyl radical production in the rat striatum during carbon monoxide poisoning

doi: 10.1038/s41598-020-59377-6

Figure Lengend Snippet: Effects of AT1R and AT2R antagonists on CO-induced cAMP production (left) and forskolin-ws-induced ˙ OH production (right). Losartan (50 μM) and PD123319 (100 μM) were dissolved in the perfusing medium and administered throughout the experimental period. Forskolin-ws (5 nmol/μL) was dissolve in sterilized saline and administered into the striatum at 0.1 µL/min for 10 min. The inserted graphs depict basal cAMP production (left) and basal ˙ OH production in terms of 2,3-DHBA formation (right). Each column or symbol with a vertical bar indicates the mean ± SEM. The horizontal bars indicate 40-min exposure to 3000 ppm CO (left) or administration of 5 nmol forskolin-ws (right). *Significant difference (p < 0.05) from “None” (no antagonists) by one-way ANOVA followed by Dunnett’s test.

Article Snippet: PD123319, ZD7155, A779, SR202 and EHT1864 were purchased from Tocris Bioscience (Bristol, UK).

Techniques: Saline

(A-D) Distance mapping of AT1R conformations based on the four NNMF components: (A) Aclosed (NNMF I), (B) Aoccl1 (NNMF II), (C) Aoccl2 (NNMF III), and (D) Aopen (NNMF IV). Colored surfaces reflect spin densities based on major distance peaks selected from the NNMF distributions. A representative frame from molecular dynamics simulations of ZD7155-bound AT1R is overlaid in gray. Colored arrows represent changes in label positions relative to the Aclosed map (light gray surfaces in (B), (C), and (D)).

Journal: Cell

Article Title: Angiotensin analogs with divergent bias stabilize distinct receptor conformations

doi: 10.1016/j.cell.2018.12.005

Figure Lengend Snippet: (A-D) Distance mapping of AT1R conformations based on the four NNMF components: (A) Aclosed (NNMF I), (B) Aoccl1 (NNMF II), (C) Aoccl2 (NNMF III), and (D) Aopen (NNMF IV). Colored surfaces reflect spin densities based on major distance peaks selected from the NNMF distributions. A representative frame from molecular dynamics simulations of ZD7155-bound AT1R is overlaid in gray. Colored arrows represent changes in label positions relative to the Aclosed map (light gray surfaces in (B), (C), and (D)).

Article Snippet: Related to Figure 2. (A-C) Molecular dynamics simulations of the AT1R bound to ZD7155, starting with the 4YAY crystal structure (gray).

Techniques: