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Figure 1 Intracellular signaling pathway of nitric oxide (NO), prostanoids, and natriuretic peptides: role of phosphodiesterases (PDEs). Ligands (i.e., NO, atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], and prostanoids) activate membrane-bound or soluble cyclases. Guanylate and adenylate cyclases generate cyclic guanosine monophosphate (cGMP) and adenosine monophosphate (cAMP) from GTP and ATP. These intracellular second messengers, via activation of protein kinases, induce cellular responses (i.e., vasodilation and anti-proliferation). Phosphodiesterases limit the effects of the ligands by degradation of second messengers cGMP and cAMP into inactive GMP and AMP. Thus, by inhibition of the PDEs, the PDE inhibitors augment and prolong the cellular responses to NO, prostanoids, and natriuretic peptides.
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