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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]
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.
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.
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.
The elevation of intracellular cGMP results in relaxation by the activation of cGMP-dependent protein kinase, which phosphorylates target proteins such as the myosin phosphatase-targeting subunit (MYPT) and the IP3 receptor-associated cGMP kinase substrate (IRAG). In addition, cGMP has been proposed to also cause smooth muscle relaxation ...
Myosin light chains are involved in smooth muscle contraction. The result is vascular smooth muscle relaxation, which allow vessels to dilate. [ 34 ] This mechanism is similar to that of phosphodiesterase 5 (PDE5) inhibitors such as sildenafil (Viagra) and tadalafil (Cialis), which elevate cGMP concentration by inhibiting its degradation by PDE5.
In addition to human corpus cavernosum smooth muscle, PDE5 is also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle. The inhibition of PDE5 in these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in ...
Six type 2 (bitter) taste receptors (TAS2Rs) are expressed by airway smooth muscle cells. In the tongue, bitter taste receptors have probably evolved for avoiding the ingestion of plant toxins. In the lungs, bitter taste receptors serve a paradoxically reversed function, causing the relaxation of airway smooth muscle, i.e., a lowering of airway ...