5-HYDROXYTRYPTAMINE(2)-FAMILY RECEPTORS (5-HYDROXYTRYPTAMINE(2A), 5-HYDROXYTRYPTAMINE(2B), 5-HYDROXYTRYPTAMINE(2C)) - WHERE STRUCTURE MEETSFUNCTION

5-Hydroxytryptamine(2) (serotonin(2), 5-HT2)-family receptors are impo rtant for mediating many physiological functions, including vascular a nd nonvascular smooth muscle contraction, platelet aggregation, modula tion of perception, mood, anxiety, and feeding behavior. A large numbe r of psychopharmaceuticals, including atypical antipsychotic drugs, an tidepressants, anxiolytics, and hallucinogens, mediate their actions, at least in part, via interactions with various 5-HT2-family receptors . This review article summarizes information about structure function aspects of 5-HT2-family receptors. Evidence is presented that implies that conserved aromatic and charged residues are essential for ligand binding to 5-HT2A receptors. Additionally, findings are reviewed that are consistent with the hypothesis that residues located in intracellu lar loops 2 and 3 (i2 and i3) mediate coupling to specific G(alpha)-su bunits such as G(alpha q). Studies are reviewed that suggest that 5-HT 2-family receptors may be down-regulated by both agonists and antagoni sts, and usually this down regulation is due to post-transcriptional m echanisms. Finally, a model for regulation of 5-HT2-family receptors b y receptor mediated endocytosis is advanced, and the particular struct ural features responsible for the various endocytotic pathways are emp hasized. Taken together, these results suggest that discrete domains o f the receptor structure are important for ligand binding, G-protein c oupling, and internalization. (C) 1998 Elsevier Science Inc.