Open Access
Discovery of the nitric oxide signaling pathway and targets for drug development
Nathan S Bryan1,Ka Bian1,Ferid Murad1
Institute of Molecular Medicine, The University of Texas-Houston Health Sciences Center, Houston, TX 77030, USA
DOI: 10.2741/3228 Volume 14 Issue 1, pp.1-18
Published: 01 January 2009
(This article belongs to the Special Issue Nitric oxide, superoxide and peroxynitrite in cardiovascular diseases)

Nitric oxide is a multifunctional signaling molecule, intricately involved with maintaining a host of physiological processes including but not limited to host defense, neuronal communication and the regulation of vascular tone. Many of the physiological functions first ascribed to NO are mediated through its primary receptor, soluble guanylyl cyclase. Endogenous production of NO is a highly complex and regulated process involving the 5-electron oxidation of L-arginine requiring numerous substrates and cofactors. The production of a highly reactive and diffusible free radical gas further complicates our established concept and model of specific and targeted receptor-ligand interaction to elicit cell signaling events. Hence there are many steps in the endogenous pathway for altered production of NO and subsequent activation of sGC that may be targets for drug development as well as other molecular targets for NO. The following review will highlight the current state of the art of NO-sGC research and illustrate disease processes which may benefit from novel drug development exploiting the NO-sGC pathway as well as NOS and cGMP-independent pathways.

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Nathan S Bryan, Ka Bian, Ferid Murad. Discovery of the nitric oxide signaling pathway and targets for drug development. Frontiers in Bioscience-Landmark. 2009. 14(1); 1-18.