Regulation of cyclic GMP and cyclic AMP production by S-nitroso-cysteine in rat thymocytes.
Nitrogen monoxides regulate cellular functions via cyclic GMP accumulation induced by nitric oxide (NO). However, the effects of NO on the cyclic AMP system have not been studied in detail. In this study, we investigated the effects of various NO donors on cyclic GMP and cyclic AMP accumulation in rat thymocytes. Addition of S-nitroso-cysteine stimulated cyclic GMP accumulation at concentrations up to 10 microM, but was inhibitory at higher concentrations. Other NO donors such as sodium nitroprusside stimulated cyclic GMP accumulation markedly without causing 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-cysteine on cyclic AMP accumulation in membranes was partially reversed by dithiothreitol treatment. These findings suggest that the cyclic AMP system in thymocytes is specifically modified by S-nitroso-cysteine, and not by the NO/cyclic GMP system.
Miyakoshi
M
M
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Yamada
T
T
Katayama
H
H
Murayama
T
T
Nomura
Y
Y
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D009603:Nitroso Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D013439:Sulfhydryl Reagents; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D000242:Cyclic AMP; D006152:Cyclic GMP; D003545:Cysteine; D004229:Dithiothreitol