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Publisher Summary This chapter covers the general topic of nitric oxide (NO) and cGMP-mediated signaling, while focusing on a few recent interesting findings. Research and interest in NO-related signaling and its connection to cGMP are increasing constantly. NO and cGMP constitute an autocrine, paracrine, and possibly endocrine signal transduction system. Cytosolic NO-responsive guanylate cyclase can be stimulated by NO derived from its own cell, from similar or distinct neighboring cell types within a tissue, from a circulating pool of NO (as NO + equivalents coupled to plasma protein thiol groups), or from pharmacological agents, the nitrovasodilators. Signaling through cAMP and NO/cGMP pathways is interconnected at the level of control of the various isoforms of cyclic nucleotide phosphodiesterases (PDEs). In frog ventricular myocytes Ca 2+ current ( I ca ) through the L-type Ca 2+ channel is regulated by CAMP-dependent kinase phosphorylation; these cells also contain NO-responsive guanylate cyclase and several isoforms of cyclic nucleotide PDEs. In a number of tissues, NO and cGMP signaling has active cross-talk with other important signaling pathways and second messengers. NO and cGMP together compose an especially wide-ranging signal transduction system when the many roles of cGMP in physiological regulation are considered, including smooth muscle relaxation, visual transduction, intestinal ion transport, and platelet function, the many sources, biochemical interactions, and functions of NO, and the interactions of cGMP and its affected pathways with other signaling systems, such as phophoinositides, eicosanoids, cAMP, and Ca 2+ . |
