Involvement of sulfhydryl groups in the oxidative modulation of particulate lung guanylate cyclase by nitric oxide and N-methyl-N'nitro-N-nitrosoguanidine.
Particulate guanylate cyclase from rat lung was activated by nitric oxide or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in a dose-dependent manner that was enhanced by dithiothreitol. Nitric oxide-stimulated guanylate cyclase activity decayed during a 60-min preincubation at 37 degrees, but did not decay at 24 degrees or 4 degrees. Dithiothreitol enhanced the decay of nitric oxide-stimulated enzyme at all temperatures by potentiating the reversal of nitric oxide activation. Following the reversal of nitric oxide activation at 24 degrees by dithiothreitol, the particulate enzyme could be reactivated by a second exposure to nitric oxide. Preincubation of basal particulate guanylate cyclase activity at 37 degrees resulted in the loss of enzyme responsiveness to activation by nitric oxide or MNNG that was potentiated by diamide or oxidized glutathione. The inhibitory effects of the thiol oxidants on enzyme responsiveness to activation by MNNG were prevented by dithiothreitol. The results suggest that activation of particulate guanylate cyclase by nitric oxide or MNNG involves the oxidation of key enzyme sulfhydryl groups.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism*; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013696:Temperature
D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D008769:Methylnitronitrosoguanidine; D009569:Nitric Oxide; D006162:Guanylate Cyclase