CHARACTERIZATION OF HUMAN 5-HYDROXYTRYPTAMINE(2A) AND 5-HYDROXYTRYPTAMINE(2C) RECEPTORS EXPRESSED IN THE HUMAN NEUROBLASTOMA CELL-LINE SH-SY5Y - COMPARATIVE STIMULATION BY HALLUCINOGENIC DRUGS

Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine(2A) (5-HT2A) or 5-HT2C receptor cDNA pro duced cell lines demonstrating ligand affinities that correlated close ly with those for the corresponding endogenous receptors in human fron tal cortex and choroid plexus, respectively. Stimulation of the recomb inant receptors by 5-HT induced phosphoinositide hydrolysis with highe r potency but lower efficacy at the 5-HT2C receptor (pEC(50) = 7.80 +/ - 0.06) compared with the 5-HT2A receptor (pEC(50) = 7.30 +/- 0.08), A ctivation of the 5-HT2A receptor caused a transient fourfold increase in intracellular Ca2+ concentration, Whole-cell recordings of cells cl amped at -50 mV demonstrated a small inward current (2 pA) in response to 10 mu M 5-HT for both receptors. There were no differences in pote ncy or efficacy of phosphoinositide hydrolysis among four hallucinogen ic [d-lysergic acid diethylamide (LSD), 1-(4-iodo-2,5-dimethoxyphenyl) -2-aminopropane (DOI), 5-methoxy-N,N-dimethyltryptamine, and mescaline ] and three nonhallucinogenic drugs (m-chlorophenylpiperazine, quipazi ne, and ergotamine). Comparison of equipotent doses producing 20% of t he maximal response induced by 5-HT revealed selective activation of t he 5-HT2A receptor by LSD and to a lesser degree by DOI, mescaline, an d ergotamine. Quipazine and 5-methoxy-N,N-dimethyltryptamine were rela tively nonselective, whereas m-chlorophenylpiperazine selectively acti vated the 5-HT2C receptor, It is unlikely therefore that hallucinosis is mediated primarily by activity at the 5-HT2C receptor, whereas acti vity at the 5-HT2A receptor may represent an important but not unique mechanism associated with hallucinogenic drug action.