Serotonin 5-HT2A receptors: Molecular biology and mechanisms of regulation

Serotonin 5-HT2A receptors are essential for a large number of physiologica l functions in the central nervous system and periphery. This review articl e summarizes our current knowledge of the molecular biology and mechanisms of regulation of 5-HT2A receptors. The mode of drug binding using data deri ved from molecular modeling and site-directed mutagenesis is described. The cellular and subcellular localization of 5-HT2A receptors is described, an d the concentration of 5-HT2A receptors on apical dendrites of pyramidal ne urons is emphasized. Various modes of regulation of 5-HT2A receptors are al so summarized, including transcriptional, post-translational and mRNA editi ng processes. Finally, an integrated model of 5-HT2A receptor regulation th at involves various protein kinases (protein kinase C, G-protein receptor k inases), arrestins, clathrin-coated vesicles, endosomes and lysosomes. The relevance of these pathways for antidepressant and antipsychotic drug actio ns is emphasized.