Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sesquiterpene polygodial produces graded relaxation in rings of rabbit pulmonary artery or thoracic aorta and guinea-pig pulmonary artery with endothelium. In rings with rubbed endothelium its vasorelaxant action was largely reduced. The N(omega)-nitro-L-arginine (L-NOARG), N(G)-nitro-L-arginine methyl ester (L-NAME), 6-anilino-5,8-quinolinedione (LY 83583) and 1H-[1,2, 4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), inhibited the endothelium-dependent vasorelaxant action of polygodial. In contrast, N(omega)-nitro-D-arginine (D-NOARG), indomethacin, N(2)-[(4R)-4-hydroxy-1-(1methyl-1H-indol-3yl)carbonyl-L-prol yl]-N-met hyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide (FK 888), (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3, 4-dichlorophenyl)butyl]benzamide (SR 48968), (8R,9S, 11S)-(-)-9-hydroxy-9-n-hexyloxy-carbonyl-8-methyl-2,3,9, 20-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triaqzadibenzo[a, g]cycloocta[c,d,e]-trinden-1-one (KT 5720), calcitocin gene-related peptide receptor antagonist (CGRP-(8-37), apamin, charybdotoxin and 4-aminopyridine had no effect on polygodial action. However, glibenclamide inhibited partially, but significantly, its relaxant responses. These results demonstrate that the vasorelaxation of polygodial is partly dependent on the release of nitric oxide (NO )or an NO-derived substance from the vascular endothelium through an activation of a guanylyl cyclase-dependent mechanism. Finally, results demonstrate that the polygodial vasorelaxant action is not related with the opening of potassium (K(+)) channels, release of prostacyclin, substance P, or with the activation of adenylyl cyclase-dependent mechanisms.
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PMID:Mechanisms underlying the relaxation caused by the sesquiterpene polygodial in vessels from rabbit and guinea-pig. 1061 63

4-(Nitrooxy)-butyl-(S)-2-(6-methoxy-2-naphthyl)-propanoate (AZD3582) is a cyclooxygenase (COX)-inhibiting nitric oxide donator (CINOD). It donates nitric oxide (NO) in biological systems through as yet unidentified mechanisms. cGMP, a marker of intracellularly generated NO, was increased up to 27-fold over basal levels by AZD3582 (1-30microM) in LLC-PK1 kidney epithelial cells. A 5h pretreatment with glyceryl tinitrate (GTN, 0.1-1microM) attenuated the cGMP response to a subsequent challenge with AZD3582 or GTN. Similarly, AZD3582 (10-30microM) pretreatment reduced the increase in cGMP on subsequent incubation with AZD3582 or GTN. In contrast, cGMP stimulation by SIN-1, which releases NO independently of enzymatic catalysis, remained unimpaired in cells pretreated with GTN or AZD3582. Our results demonstrate that AZD3582 decreases the sensitivity of the guanylyl cyclase/cGMP system to GTN and vice versa. This suggests that bioactivation pathways for organic nitrates, which involve enzymatic catalysis, may be responsible for NO donation from AZD3582.
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PMID:A common pathway of nitric oxide release from AZD3582 and glyceryl trinitrate. 1475 6