Guanylyl cyclase, nitric oxide-dependent

Cokic VP, Smith RD, Beleslin-Cokic BB, et al. Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase. J Clin Invest 2003 111 231-239. 

Synthesized by soluble guanylyl cyclase and particulate guanylyl cyclase from guanosine triphosphate (GTP). Nitric oxide activates soluble guanylyl cyclase to enhance cyclic GMP production that contributes to various NO actions. Cyclic GMP is hydrolyzed by phosphodiesterases. Cyclic GMP binds to and activates cGMP-dependent protein kinase, phosphodiesterases, and Cyclic Nucleotide-regulated Cation Channels. 

Activation of brain H receptors also stimulates cGMP synthesis [19]. Outside the brain, histamine is known to relax vascular smooth muscle by activation of endothelial H receptors, thereby increasing endothelial Ca2+ concentrations and stimulating the synthesis and release of nitric oxide. The latter, a diffusible agent, then activates the smooth muscle guanylyl cyclase [30]. Although less is known about these mechanisms in the CNS, there is evidence that brain H receptor activation can produce effects that depend on guanylyl cyclase activity [19]. 

Fig. 9.1 Nitric oxide mediated inhibition of platelet activation. Abbreviations used NO, nitric oxide EDRF, endothelium-derived relaxing factor GC, guanylyl cyclase PDE, phosphodiesterase cGMP-PK, GMP-dependent protein kinase Raplb, small GTPase Raplb ...

In contrast, the soluble guanylyl cyclases are regulated by nitric oxide and NO-forming drugs through the Caz+ calmodulin-dependent nitric oxide synthase. 

Gage AT, Reyes M, Stanton PK (1997) Nitric-oxide-guanylyl-cyclase-dependent and -independent components of multiple forms of long-term synaptic depression. Hippocampus 7 286-95... 

NO), which activates cGMP-dependent protein kinase through stimulation of guanylyl cyclase and elevation of cGMP, relaxes arteries. Nitric oxide has also been reported to activate K channels directly in aortic smooth muscle (Bolotina et al., 1994), as well as activate K jp channels in rabbit mesenteric arteries (Murphy and Brayden, 1995). 

Ferrero R, Rodriguez-Pascual F (2000) Nitric oxide-sensitive guanylyl cyclase activity inhibition through cyclic GMP-dependent dephosphorylation. J Neurochem 75 2029-2039... 

Fig. 76.2 Polyphenols and polyphenol-rich sources induce endothelial-dependent NO- and EDH-mediated relaxations. Polyphenols are potent inducers of the oidothelial formation of nitric oxide (NO) and endothelium-derived hyperpolarizatitm (EDH) via a redox-soisitive mechanism. SKca small conductance calcium-activated potassium channels, IKca intermediate conductance calcium-activated potassium channels, Src Src family kinase, PI3K phosphatidylinositol 3-kinase, eNOS endothelial NO synthase, L-Arg L-arginine, sGC soluble guanylyl cyclase, GTP guanosine triphosphate, cGMP cyclic guanosine monophosphate, AA arachidonic acid, COX cyclooxygenase, ATP adenosine triphosphate, cAMP cyclic adenosine monophosphate...

Ridnour, L.A., Windhausen, A.N., Isenberg, J.S., Yeung, N., Thomas, D.D., Vitek, M.P., Roberts, D.D., Wink, D.A. (2007). Nitric oxide regulates matrix metalloproteina.se-9 activity by guanylyl-cyclase-dependent and -independent pathways. Proc. Natl. Acad. Sci. USA 104(43) 16898-16903. 

Zabel, U., Kleinschnitz, C., Oh, P, Nedvetsky, R, Smolenski, A., Muller, H., Kronich, P., Kugler, P, Walter, U., Schnitzer, J.E., and Schmidt, H.H. (2002). Calcium-dependent membrane association sensitizes soluble guanylyl cyclase to nitric oxide. Nat. Cell. Biol. 4, 307-311. 

Takabuchi, S., Hirota, K., Nishi, K., et al. (2004). The inhibitory effect of sodium nitropmsside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway. Biochem. Bioph. Res. Co. 324, 417 23. 

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