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cGMP-dependent protein kinase or protein kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle relaxation, platelet function, sperm metabolism, cell division, and nucleic acid synthesis.
Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP.Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface. [1]
[21] [28] [29] Cyclic GMP binds to the cGMP-dependent protein kinase (PKG1) which phosphorylates several proteins that results in decreased intracellular calcium. Lower intracellular calcium leads to smooth muscle relaxation and ultimately penile erection. This pathway is demonstrated in figure 1. [29] [30]
In smooth muscle, cGMP is the signal for relaxation, and is coupled to many homeostatic mechanisms including regulation of vasodilation, vocal tone, insulin secretion, and peristalsis. Once formed, cGMP can be degraded by phosphodiesterases, which themselves are under different forms of regulation, depending on the tissue.
PDE5 normally breaks down cGMP, which is responsible for arterial smooth muscle relaxation. By preventing PDE5 from working properly, cGMP stays elevated and Viagra essentially gives blood a green ...
In addition, cGMP has been proposed to also cause smooth muscle relaxation indirectly by increasing levels of cAMP. [83] When inhaled, nitric oxide dilates the pulmonary vasculature and, because of efficient scavenging by hemoglobin, has minimal effect on the vasculature of the entire body. [84]
This dilates blood vessels by relaxing smooth muscle in their linings. eNOS is the primary controller of smooth muscle tone. NO activates guanylate cyclase, which induces smooth muscle relaxation by: Increased intracellular cGMP, which inhibits calcium entry into the cell, and decreases intracellular calcium concentrations
Smooth muscle tissue is mostly made of actin and myosin, [3] two proteins that interact together to produce muscle contraction and relaxation. Myosin II, also known as conventional myosin, has two heavy chains that consist of the head and tail domains and four light chains (two per head) that bind to the heavy chains in the “neck” region.