Serotonin 5-HT2A receptors: molecular biology and mechanisms of regulation.
Serotonin 5-HT2A receptors are essential for a large number of physiological functions in the central nervous system and periphery. This review article summarizes our current knowledge of the molecular biology and mechanisms of regulation of 5-HT2A receptors. The mode of drug binding using data derived from molecular modeling and site-directed mutagenesis is described. The cellular and subcellular localization of 5-HT2A receptors is described, and the concentration of 5-HT2A receptors on apical dendrites of pyramidal neurons is emphasized. Various modes of regulation of 5-HT2A receptors are also summarized, including transcriptional, post-translational and mRNA editing processes. Finally, an integrated model of 5-HT2A receptor regulation that involves various protein kinases (protein kinase C, G-protein receptor kinases), arrestins, clathrin-coated vesicles, endosomes and lysosomes. The relevance of these pathways for antidepressant and antipsychotic drug actions is emphasized.
Roth
B L
BL
Department of Psychiatry, Case Western Reserve University Medical School, Cleveland, OH 44106, USA.
Berry
S A
SA
Kroeze
W K
WK
Willins
D L
DL
Kristiansen
K
K
D000818:Animals; D003863:Depression / Q000209:etiology; D006801:Humans; D011494:Protein Kinases / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D012559:Schizophrenia / Q000209:etiology; D018490:Serotonin Agents / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects
D011985:Receptors, Serotonin; D018490:Serotonin Agents; D014157:Transcription Factors; D011494:Protein Kinases