Molecular pathopharmacology of 5-HT2C receptors and the RNA editing in the brain

J Pharmacol Sci. 2006;100(5):427-32. doi: 10.1254/jphs.cpj06005x.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Adenosine Deaminase / metabolism
  • Animals
  • Brain / metabolism*
  • Depression / chemically induced
  • Depressive Disorder / drug therapy
  • Depressive Disorder / etiology
  • Humans
  • Models, Biological
  • RNA Editing / drug effects
  • RNA Editing / genetics*
  • RNA, Messenger / metabolism
  • Receptor, Serotonin, 5-HT2C / genetics*
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Serotonin / genetics*
  • Serotonin / metabolism
  • Serotonin Receptor Agonists / pharmacology
  • Signal Transduction / drug effects

Substances

  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2C
  • Serotonin Receptor Agonists
  • Serotonin
  • Adenosine Deaminase