Sulfhydryl group involvement in the modulation of guanosine 3′,5′-monophosphate metabolism by nitric oxide, norepinephrine, pyruvate and t-butyl hydroperoxide in minced rat lung

Abstract

The cyclic GMP content of rat lung mince was increased nearly 50-fold within 4 sec following exposure to nitric oxide. This rapid increase in cyclic GMP accumulation was prevented by 10 mM, but not 1 mM, dithiothreitol which itself caused a slower yet massive (100-fold) increase in the cyclic GMP content of lung mince. Tissue cyclic GMP following nitric oxide exposure declined rapidly even in the presence of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine. The decline in cyclic GMP was accelerated by the thiol oxidant diamide (1 mM). The cyclic GMP content of lung mince was also increased by norepinephrine, pyruvate and t-butyl hydroperoxide. Diamide blocked cyclic GMP accumulation in response to these other agents as well as that caused by nitric oxide or dithiothreitol. The results suggest that sulfhydryl group modification may be a common pathway for the enhancement of cyclic GMP synthesis in tissues by a variety of stimuli.