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Concept
Cyclic guanosine monophosphate
Summary
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. Through protein kinases activation, cGMP can relax smooth muscle. cGMP concentration in urine can be measured for kidney function and diabetes detection.
Guanylate cyclase (GC) catalyzes cGMP synthesis. This enzyme converts GTP to cGMP. Peptide hormones such as the atrial natriuretic factor activate membrane-bound GC, while soluble GC (sGC) is typically activated by nitric oxide to stimulate cGMP synthesis. sGC can be inhibited by ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one).
cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. It also relaxes smooth muscle tissues. In blood vessels, relaxation of vascular smooth muscles leads to vasodilation and increased blood flow. At presynaptic terminals in the striatum, cGMP controls the efficacy of neurotransmitter release.
cGMP is a secondary messenger in phototransduction in the eye. In the photoreceptors of the mammalian eye, the presence of light activates phosphodiesterase, which degrades cGMP. The sodium ion channels in photoreceptors are cGMP-gated, so degradation of cGMP causes sodium channels to close, which leads to the hyperpolarization of the photoreceptor's plasma membrane and ultimately to visual information being sent to the brain.
cGMP is also seen to mediate the switching on of the attraction of apical dendrites of pyramidal cells in cortical layer V towards semaphorin-3A (Sema3a). Whereas the axons of pyramidal cells are repelled by Sema3a, the apical dendrites are attracted to it. The attraction is mediated by the increased levels of soluble guanylate cyclase (SGC) that are present in the apical dendrites. SGC generates cGMP, leading to a sequence of chemical activations that result in the attraction towards Sema3a.
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