Adenosine 3',5'-monophosphate formation by preparations of rat liver soluble guanylate cyclase activated with nitric oxide, nitrosyl ferroheme, S-nitrosothiols, and other nitroso compounds

Canadian Journal of Physiology and Pharmacology
D B McNamaraL J Ignarro

Abstract

Cyclic AMP formation from ATP was stimulated by unpurified and partially purified soluble hepatic guanylate cyclase in the presence of nitric oxide (NO) or compounds containing a nitroso moiety such as nitroprusside, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), nitrosyl ferroheme, and S-nitrosothiols. Cyclic AMP formation was undetectable in the absence of NO or nitroso compounds and was not stimulated by fluoride or glucagon, indicating the absence of adenylate cyclase activity. The nitroso compounds failed to activate, whereas fluoride or glucagon activated, adenylate cyclase in washed rat liver membrane fractions. Cyclic GMP formation from GTP was markedly stimulated by the soluble hepatic fraction in the presence of NO or nitroso compounds. Cyclic AMP formation by partially purified guanylate cyclase was competitively inhibited by GTP and cyclic GMP formation is well-known to be competitively inhibited by ATP. Therefore, it appears that activated guanylate cyclase, rather than adenylate cyclase, was responsible for the formation of cyclic AMP from ATP. Formation of cyclic AMP of cyclic GMP was enhanced by thiols, inhibited by hemoproteins and oxidants, and required the addition of either Mg2+ or Mn2+. Further, several nitros...Continue Reading

Citations

Apr 7, 2012·Critical Care Research and Practice·Bobby NossamanPhilip Kadowitz
Jun 29, 2004·The American Journal of Cardiology·Ferid Murad
Mar 31, 2004·Nitric Oxide : Biology and Chemistry·H P MonteiroA Stern
Aug 22, 2013·Angewandte Chemie·Markus FollmannAlexander Straub
Mar 25, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Edward A PankeyPhilip J Kadowitz

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