Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor
Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor
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安非他明、3,4-亚甲二氧基甲基苯丙胺、麦角酸二乙酰胺和儿茶酚胺神经递质的代谢物是大鼠微量胺受体的激动剂
DOI：
10.1124/mol.60.6.1181
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发表时间：
2001-12-01
影响因子：
3.6
通讯作者：
Grandy, DK
中科院分区：
文献类型：
--
作者：
Bunzow, JR;Sonders, MS;Grandy, DK
微量胺对酪胺在结构和功能上与安非他明和生物胺神经递质相关。目前认为，微量胺如对酪胺和精神兴奋剂安非他明引起的生物活性是其抑制细胞外递质清除和/或刺激递质从细胞内储存流出的能力的表现。在这里，我们报告的发现和药理学特性的大鼠G蛋白偶联受体，刺激cAMP的产生时，暴露于微量胺p-酪胺，β-苯乙胺，色胺，章鱼胺。一项广泛的药理学研究表明，精神兴奋剂和致幻安非他明，许多麦角林衍生物，肾上腺素能配体，和3-甲基化代谢物的儿茶酚胺神经递质也是良好的激动剂在大鼠痕量胺受体1（rTAR 1）。这些结果表明，微量胺和儿茶酚胺代谢产物可能作为一种新的细胞间信号系统的内源性配体广泛发现整个脊椎动物的大脑和外周。此外，安非他明，包括3，4-亚甲二氧基甲基安非他明（MDMA;“摇头丸”），是有效的rTAR 1激动剂的发现表明，这些广泛使用的药物的作用可能部分是由这种受体以及它们以前表征的靶点，神经递质转运蛋白介导的。
The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta -phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.