Stimulation of soluble coronary arterial guanylate cyclase by SIN-1.
SIN-1, a metabolite of the vasodilating drug molsidomine, was found to stimulate dose dependently (0.01-1 mM) soluble guanylate cyclase from bovine coronary arteries up to 100-fold the control value. The stimulatory effect of SIN-1 increased with rising concentrations of MnC1(2) or MgC1(2) and was diminished in the presence of methylene blue or ferricyanide. The time course of SIN-1-induced guanylate cyclase stimulation was characterized by a lag phase which was not observed after preincubation of the enzyme with SIN-1. In contrast to nitroglycerin and sodium nitroprusside, SIN-1 did not require the presence of cysteine or other thiols to stimulate guanylate cyclase. The results presented in this study provide further evidence that SIN-1 exerts its dilating effect on coronary vessels via direct stimulation of guanylate cyclase.
Schmidt
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Kukovetz
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D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis; D005292:Ferricyanides / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D012977:Sodium Nitrite / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013558:Sydnones / Q000494:pharmacology*
D002413:Cations, Divalent; D005292:Ferricyanides; D010069:Oxadiazoles; D013438:Sulfhydryl Compounds; D013558:Sydnones; C007931:hexacyanoferrate III; D009599:Nitroprusside; C002385:linsidomine; D008981:Molsidomine; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP; D012977:Sodium Nitrite; D008751:Methylene Blue