Cyclic GMP metabolism and its role in brain physiology.
Cyclic GMP (cGMP) is synthesized by guanylyl cyclase (GC) in response to nitric oxide (NO) and carbon monoxide (CO) or natiuretic peptides (NPs); atrial, brain and C-type (ANP, BNP and CNP). cGMP is degraded by several cGMP-specific phosphodiesterases (PDEs). Guanylate cyclases (GC) are differentiated into: membrane-bound/particulate (pGC) and cytosolic/soluble (sGC). In recent years evidence has accumulated that NO is the main activator of sGC and NO/cGMP plays important role in glutaminergic, cholinergic and dopaminergic signaling pathways. cGMP in the nervous system is involved in long term potentiation and depression (LTP, LTD) suggesting its participation in learning and memory mechanism. cGMP regulates calcium homeostasis and phototransduction. Its level is regulated by PDEs and their specific inhibitors protect cGMP level in cells and are very important from clinical point of view.
Domek-Łopacińska
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K
Department of Cellular Signaling, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. kdomek@cmdik.pan.pl
Strosznajder
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JB
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007858:Learning; D008568:Memory; D009473:Neuronal Plasticity; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D015290:Second Messenger Systems / Q000187:drug effects; D014785:Vision, Ocular
D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D017869:Cyclic GMP-Dependent Protein Kinases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000109:Acetylcholine; D002118:Calcium