Guanylate cyclase by nitric oxide

Gruetter, C. A., Barry, B. K., McNamara, D. B., Gruetter, D. Y., Kadowitz, P. J., and Ignarro, L. J. (1979). Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoam-ine. ]. Cyclic Nucleotide Protein Phosphorylation Res. 5, 211-224. 

Ignarro, L. J., Degnan, J. N., Baricos, W. H., Kadowitz, P. J., and Wolin, M. S. (1982a). Activation of purified guanylate cyclase by nitric oxide requires heme Comparison of heme-deficient, heme-reconstituted and heme-containing forms of soluble enzyme from bovine lung. Biochim. Biophys. Acta 718, 49-59. 

Stone JR, Marietta MA. Spectral and kinetic studies on the activation of soluble guanylate cyclase by nitric oxide. Biochemistry 1996 35 1093-1099. 

Ignarro, L. J. (1992). Haem-dependeht activation of cytosolic guanylate cyclase by nitric oxide A widespread signal transduction mechanism. Biochem. Soc. Trans. 20(2), 465-469. 

Craven, P. A., and DeRubertis, F. R. (1983). Requirement of heme in the activation of purified guanylate cyclase by nitric oxide. Biochim. Biophys. Acta 745, 310-321. 

Fig. 1. Nitric oxide (NO) synthesis by nitric oxide synthase (NOS) (upper left), NO reaction with soluble guanylate cyclase (sGC) (middle), and formation of cyclic GMP, which causes tissue-specific signaling (right). The roles of the salivary nitrophorins from Rhodnius prolixus in storing and releasing NO and binding histamine are included (lower left).

Nitrosothiols should not bind directly to the heme of guanylate cyclase, but rather to activate guanylate cyclase by releasing nitric oxide. The simple cleavage of nitrosothiols into nitric oxide and a thiol radical is energetically expensive, so the activation may involve an oxidation with a second thiol group. 

Guanylate cyclases, which form cyclic GMP, occur in particulate and soluble forms.908 The latter have been of great interest because they are activated by nitric oxide (NO). The soluble guanylate cyclases are a(3 heterodimers. The C-terminal regions of both a and (3 subunits are homologous to the catalytic domain of adenylate cyclase. The N-terminal domain of the a subunits contains heme whose Fe atom is coordinated... 

Marsault R, Frelin C (1992) Activation by nitric oxide of guanylate cyclase in endothelial cells from brain capillaries. J Neurochem 59 942-945. 

Soluble guanylate cyclase is activated by nitric oxide (NO) (see Section 3.4). NO has been implicated in the generation of long term depression (LTD) of parallel fiber-mediated EPSP s in Purkinje cells. LTD can be prevented by the application of haemoglobin that absorbs NO, or by the inhibition of NO synthesis (Crepel and Jaillard, 1990 Shibuki and Okada, 1991 Ito, 1991). However, nitric oxide synthase, the synthesizing enzyme of NO, appears to be absent from the Purkinje cell (Section 3.4.). 

Katsuki, S., Arnold, W., Mittal, C. K., and Murad, F. (1977a). Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. /. Cyclic Nucleotide Res. 3, 23-35. 

Zhao Y, Hoganson C et al (1998) Structural changes in the heme proximal pocket induced by nitric oxide binding to soluble guanylate cyclase. Biochemistry 37 12458-12464... 

Acetylcholine-mediated parasympathetic activity leads to production of the non-adrenergic-non-cholinergic transmitter nitric oxide. By enhancing the activity of guanylate cyclase, nitric... 

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

A special guanylate cyclase receptor can be found in the nitric oxide (NO) signaling pathway. The activation of the sequence of events in that pathway results in smooth muscle relaxation. This pathway is directly linked to other cascades by receiving a Ca2+ signal and utilizing calmodulin (CaM) as transmitter protein. 

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