Amino acids in transmembrane domain two influence anesthetic enhancement of serotonin-3A receptor function

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• 作者：Lopreato ; Gregory F. ; Banerjee ; Paula ; Mihic ; S. John
• 关键词：Neurotransmitters ; modulators ; transporters and receptors ; Serotonin receptors ; Anesthetic ; Alcohol ; Electrophysiology ; Xenopus oocytes ; Serotonin-3A receptor mutants ; 5-HT_3A
• 刊名：Molecular Brain Research
• 出版年：2003
• 出版时间：October 21, 2003
• 年：2003
• 卷：118
• 期：1-2
• 页码：45-51
• 全文大小：199 K

文摘

Alcohols and volatile anesthetics affect the function of members of the nicotinic acetylcholine (nACh) superfamily of receptors. Studies on glycine and GABA_A receptors implicate amino acid residues within transmembrane (TM) regions two and three of these receptors as critical for alcohol and anesthetic enhancement of receptor function. The serotonin-3 (5-HT₃) receptor is a member of the nicotinic acetylcholine receptor superfamily, sharing sequence and structural homology with the other members. We tested the hypothesis that amino acids of the 5-HT₃ receptor homologous to those shown to affect alcohol and anesthetic potentiation in GABA_A and glycine receptors also determine the effects of these compounds on the 5-HT₃ receptor. Six 5-HT_3A mutant cDNAs were generated by site-directed mutagenesis of two amino acids, phenylalanine-269 (14′) and lecucine-270 (15′) in transmembrane domain two (TM2). When assayed electrophysiologically in Xenopus oocytes, wild-type 5-HT₃ receptors exhibit enhancement of function by enflurane, halothane, isoflurane, chloroform and ethanol, but not by decanol and propofol. Mutations in transmembrane domain two markedly affected alcohol and anesthetic enhancement of 5-HT₃ receptor function. Some mutations had differential effects on the abilities of the isomers enflurane and isoflurane to potentiate 5-HT₃ receptor function.