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)

1. Ethacrynic acid, an agent that alkylates sulfhydryl residues, inhibited sodium nitroprusside- and 8-bromo cyclic GMP-induced relaxations. 2. Sodium nitroprusside-induced increased levels of cyclic GMP were unaltered by ethacrynic acid. 3. Concentrations of ethacrynic acid that inhibited sodium nitroprusside-induced relaxation did not affect sodium nitroprusside-activation of crude soluble and particulate fractions of guanylate cyclase, while a higher concentration of ethacrynic acid did inhibit the activation. 4. Cystamine, an agent that oxidizes sulfhydryl residues, inhibited sodium nitroprusside-activation of crude soluble and particulate fractions of guanylate cyclase. Exposure of intact rat aorta to cystamine inhibited basal guanylate cyclase activity in the particulate fraction but, in general, not in the soluble fraction. 5. These results are consistent with the hypothesis that vascular smooth muscle relaxation requires sulfhydryl groups. The sulfhydryl groups that presumably are alkylated by ethacrynic acid are not contained within guanylate cyclase and are involved at a regulatory step after the formation of cyclic GMP. The sulfhydryl groups altered by cystamine may be located on particulate guanylate cyclase and a role for particulate guanylate cyclase in nitrovasodilator-induced relaxation needs to be examined further.
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PMID:Effects of ethacrynic acid and cystamine on sodium nitroprusside-induced relaxation, cyclic GMP levels and guanylate cyclase activity in rat aorta. 289 33

The mechanism whereby nitroglycerin relaxes vascular smooth muscle remains uncertain. A current hypothesis suggests that nitroglycerin reacts with critical cellular sulfhydryl groups to form an intermediate, which activates guanylate cyclase, resulting in cGMP accumulation and relaxation. This study investigated further the potential involvement of sulfhydryls in nitroglycerin-induced vascular smooth muscle relaxation by evaluating effects of a variety of sulfhydryl alkylating and reducing agents on responses to nitroglycerin and other relaxants in bovine coronary arterial strips submaximally contracted using 30 mM K. Whereas 10(-4) M 5,5'-dithiobis-(2-nitrobenzoic acid), 10(-5) MN-ethylmaleimide, and 10(-4) MN-naphthylmaleimide did not affect nitroglycerin-induced relaxation, 10(-4) MN-ethylmaleimide and 10(-4) M ethacrynic acid significantly inhibited relaxation induced by nitroglycerin. Both ethacrynic acid and N-ethylmaleimide at 10(-4) M also inhibited relaxation induced by sodium nitroprusside. N-ethylmaleimide, but not ethacrynic acid, inhibited relaxation induced by isoproterenol and forskolin. Ethacrynic acid significantly reduced both relaxation and cGMP elevation induced by both 10(-7) M nitroglycerin and 10(-7) M sodium nitroprusside. Ethacrynic acid, but not N-ethylmaleimide, significantly reduced relaxation induced by 8-Br-cGMP. Pretreatment with the sulfhydryl-containing agents N-acetylcysteine, 2-mercaptoethanol, or dithiothreitol, at 10(-3) M did not affect nitroglycerin-induced relaxation in nontolerant arteries. Similarly, N-acetylcysteine and dithiothreitol did not alter the depressed responses to nitroglycerin in arteries in which tolerance to nitroglycerin was induced in vitro. A slight but statistically significant reversal of nitroglycerin-tolerance occurred after treatment of tolerant arteries with 2-mercaptoethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of sulfhydryl reagents on nitroglycerin-induced relaxation of bovine coronary artery. 302 84

We examined the effect of nipradilol on contraction of the posterior ciliary artery induced by high potassium or norepinephrine and on cyclic GMP (cGMP) levels in the posterior ciliary artery of dogs. Nipradilol caused dose-dependent relaxation of KCl-and norepinephrine-induced contractions of posterior ciliary artery. The relaxant effect of nipradilol on norepinephrine-contracted ciliary artery was significantly greater than that on KCl-contracted ciliary artery. In KCl-contracted ciliary artery, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10(-4) M) did not alter the relaxant effect of nipradilol, whereas 1H-1,2,4-oxadiazolo-4,3-a-quinoxalin-1-one (ODQ, 10(-6) M) significantly inhibited this effect. Ethacrynic acid at 10(-5) M, sulfasalazine at 10(-4) M and S-decylglutathione at 10(-4) M (glutathione S-transferase inhibitors) did not inhibit the relaxant effect of nipradilol. In addition, nipradilol produced dose-dependent increases in cGMP levels in the canine posterior ciliary artery. These findings indicate that nipradilol-induced vasorelaxation in the canine posterior ciliary artery occurs via stimulation of the guanylyl cyclase-cGMP pathway.
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PMID:Nipradilol induces vasodilation of canine isolated posterior ciliary artery via stimulation of the guanylyl cyclase-cGMP pathway. 1209 33