Premium
Characterisation of Human 5‐Hydroxytryptamine 2A and 5‐Hydroxytryptamine 2C Receptors Expressed in the Human Neuroblastoma Cell Line SH‐SY5Y: Comparative Stimulation by Hallucinogenic Drugs
Author(s) -
Newton R. A.,
Phipps S. L.,
Flanigan T. P.,
Newberry N. R.,
Carey J. E.,
Kumar C.,
McDonald B.,
Chen C.,
Elliott J. M.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67062521.x
Subject(s) - mescaline , quipazine , receptor , 5 ht2 receptor , sh sy5y , 5 ht receptor , pharmacology , lysergic acid diethylamide , hallucinogen , serotonin , chemistry , serotonergic , endocrinology , medicine , biology , cell culture , biochemistry , neuroblastoma , genetics
Stable transfection of the human neuroblastoma cell line SH‐SY5Y with the human 5‐hydroxytryptamine 2A (5‐HT 2A ) or 5‐HT 2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5‐HT induced phosphoinositide hydrolysis with higher potency but lower efficacy at the 5‐HT 2C receptor (pEC 50 = 7.80 ± 0.06) compared with the 5‐HT 2A receptor (pEC 50 = 7.30 ± 0.08). Activation of the 5‐HT 2A receptor caused a transient fourfold increase in intracellular Ca 2+ concentration. Whole‐cell recordings of cells clamped at −50 mV demonstrated a small inward current (2 pA) in response to 10 µ M 5‐HT for both receptors. There were no differences in potency or efficacy of phosphoinositide hydrolysis among four hallucinogenic [ 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, quipazine, and ergotamine). Comparison of equipotent doses producing 20% of the maximal response induced by 5‐HT revealed selective activation of the 5‐HT 2A receptor by LSD and to a lesser degree by DOI, mescaline, and ergotamine. Quipazine and 5‐methoxy‐ N,N ‐dimethyltryptamine were relatively nonselective, whereas m ‐chlorophenylpiperazine selectively activated the 5‐HT 2C receptor. It is unlikely therefore that hallucinosis is mediated primarily by activity at the 5‐HT 2C receptor, whereas activity at the 5‐HT 2A receptor may represent an important but not unique mechanism associated with hallucinogenic drug action.