REGULATION OF CYCLIC-GMP AND CYCLIC-AMP PRODUCTION BY S-NITROSO-CYSTEINE IN RAT THYMOCYTES

Nitrogen monoxides regulate cellular functions via cyclic GMP accumula tion induced by nitric oxide (NO). However, the effects of NO on the c yclic AMP system have not been studied in detail. In this study, we in vestigated the effects of various NO donors on cyclic GMP and cyclic A MP accumulation in rat thymocytes. Addition of S-nitroso-cysteine stim ulated cyclic GMP accumulation at concentrations up to 10 mu M, but wa s inhibitory at higher concentrations. Other NO donors such as sodium nitroprusside stimulated cyclic GMP accumulation markedly without caus ing inhibition. S-Nitroso-cysteine, but not other NO donors, inhibited forskolin-stimulated cyclic AMP accumulation in intact thymocytes and thymocyte membrane preparations. The inhibitory effect of S-nitroso-c ysteine on cyclic AMP accumulation in membranes was partially reversed by dithiothreitol treatment. These findings suggest that the cyclic A MP system in thymocytes is specifically modified by S-nitroso-cysteine , and not by the NO/cyclic GMP system. (C) 1998 Elsevier Science B.V. All rights reserved.