Guanylate cyclase nitric oxide-mediated activation

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

Physiological sites proposed for nitric oxide action include the immune system, where nitric oxide acts as a cytostatic agent, is tumoricidal, and can inhibit viral replication. In the cardiovascular system, nitric oxide is the biological mediator of vasodilator responses to agents such as acetylcholine and bradykinin, which act as receptors on endothelial cells to activate NOS and stimulate nitric oxide production. Diffusible nitric oxide then activates guanylate cyclase in vascular smooth muscle cells, leading to the production of cyclic guano-sine monophosphate (GMP) and vasodilation. In the brain, stimulation of A-methyl-o-aspartate receptors on... 

Jadeski, L.C., Chakraborty, C., and Inla, P.K. (2003). Nitric oxide-mediated promotion of mammary tumom cell migration requires sequential activation of nitric oxide synthase, guanylate cyclase and mitogen-activated protein kinase. Int. J. Cancer 706(4), 496-504. 

In the presence of sexual stimulation, nitric oxide is released by neurons or endothelial cells in penile tissue, thereby enhancing the activity of guanylate cyclase, the enzyme responsible for the conversion of guanylate triphosphate to cGMP (Fig. 81-6). cGMP is a vasodilatory neurotransmitter in corporal tissue. Catabolism of cGMP is mediated by phosphodiesterase. 

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.). 

NO, derived from L-arginine (L-Arg) by the enzyme nitric oxide synthase (NOS), is involved in the regulation of relevant physiological and pathophysiological functions. The mechanisms by which NO exerts its effects include activation of guanylate cyclase, formation of peroxynitrite, apoptosis, and COX regulation [96]. Apoptosis induction mediated by NO involves mitochondrial depolarization and is blocked by Bcl-2 overexpression [97]. 

Endothelial, neuronal, mitochondrial, and inducible (iNOS) forms belong to the NOS family, whose activities are based on NADPH and calmodulin (Rios-Arrabal et al., 2013). eNOS modulates cancer-related processes, such as cell death, angiogenesis, and invasion, so it possesses signi cant importance in tumor development. Cyclic guanylate monosphosphate and guanylyl cyclase mediate many biochemical reactions of nitric oxide (Miguel, 2010 Rios-Arrabal et al., 2013) (Table 11.2). 

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