Molecular pathopharmacology of 5-HT2C receptors and the RNA editing in the brain.
Among the 14 kinds of serotonin (5-hydroxytryptamine, 5-HT) receptor subtypes (5-HTR), 5-HT(2C) receptor (5-HT2CR) has been intensively investigated because of its physiologically and pathophysiologically important role in the brain. 5-HT2CR has been suggested to be involved in depressive disorders based on findings from pharmacological/neurochemical/behavioral studies using autopsy preparations of humans suffering from depression, animal models of depression, and animals treated with antidepressant drugs. Recently the editing of 5-HT2CR mRNA has been reported to participate in the pathogenesis of depressive disease. The RNA editing of 5-HT2CR induced by the presumable alteration of deaminase during a pathological state in depression causes changes of a base to another base (e.g., adenosine to guanosine, cytidine to uracil (thymidine)), followed by changes in amino acids constituting the second intracellular transmembrane loop that couples G proteins. Thus 5-HT2CR receptor-mediated signal transduction is changed. In the present review, the pathopharmacological significance of 5-HT2CR in special reference to RNA editing of receptors is reviewed and discussed from the aspect of development of novel therapeutics for depression.
Tohda
Michihisa
M
Institute of Natural Medicine, University of Toyama, Japan.
Nomura
Michio
M
Nomura
Yasuyuki
Y
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003863:Depression / Q000139:chemically induced; D003866:Depressive Disorder / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D008954:Models, Biological; D017393:RNA Editing / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics* / Q000378:metabolism*; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000243:Adenosine Deaminase