5-HT2A and 5-HT2C receptors and their atypical regulation properties.
The 5-HT(2A) and 5-HT(2C) receptors belong to the G-protein-coupled receptor (GPCR) superfamily. GPCRs transduce extracellular signals to the interior of cells through their interaction with G-proteins. The 5-HT(2A) and 5-HT(2C) receptors mediate effects of a large variety of compounds affecting depression, schizophrenia, anxiety, hallucinations, dysthymia, sleep patterns, feeding behaviour and neuro-endocrine functions. Binding of such compounds to either 5-HT(2) receptor subtype induces processes that regulate receptor sensitivity. In contrast to most other receptors, chronic blockade of 5-HT(2A) and 5-HT(2C) receptors leads not to an up- but to a (paradoxical) down-regulation. This review deals with published data involving such non-classical regulation of 5-HT(2A) and 5-HT(2C) receptors obtained from in vivo and in vitro studies. The underlying regulatory processes of the agonist-induced regulation of 5-HT(2A) and 5-HT(2C) receptors, commonly thought to be desensitisation and resensitisation, are discussed. The atypical down-regulation of both 5-HT(2) receptor subtypes by antidepressants, antipsychotics and 5-HT(2) antagonists is reviewed. The possible mechanisms of this paradoxical down-regulation are discussed, and a new hypothesis on possible heterologous regulation of 5-HT(2A) receptors is proposed.
Van Oekelen
Dirk
D
Johnson and Johnson Pharmaceutical, p/a Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Luyten
Walter H M L
WH
Leysen
Josée E
JE
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D019204:GTP-Binding Proteins