Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor

被引:482
作者
Bunzow, JR
Sonders, MS
Arttamangkul, S
Harrison, LM
Zhang, G
Quigley, DI
Darland, T
Suchland, KL
Pasumamula, S
Kennedy, JL
Olson, SB
Magenis, RE
Amara, SG
Grandy, DK
机构
[1] Oregon Hlth & Sci Univ, Sch Med, Dept Physiol & Pharmacol L334, Portland, OR 97201 USA
[2] Oregon Hlth & Sci Univ, Sch Med, Dept Mol & Med Genet, Portland, OR 97201 USA
[3] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA
[4] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97201 USA
[5] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada
关键词
D O I
10.1124/mol.60.6.1181
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1181 / 1188
页数:8
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