Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor
James R. Bunzow, Mark S. Sonders, Seksiri Arttamangkul, Laura M. Harrison, Ge Zhang, Denise I. Quigley, Tristan Darland, Katherine L. Suchland, Shailaja Pasumamula, James L. Kennedy, Susan B. Olson, R. Ellen Magenis, Susan Amara, David K. Grandy
Molecular Pharmacology December 1, 2001 DOI: 10.1124/mol.60.6.1181 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pharmacological characterization Peer reviewed |
|---|---|
| Population | Rat G protein-coupled receptor |
| Topics | LSD MDMA |
| Keywords | Amphetamine Pharmacology Amine gas treating Catecholamine Biogenic amine Receptor Biochemistry Neurotransmitter Dopamine |
| Citations | 644 |
| Key points | A rat G protein-coupled receptor (rTAR1) is activated by trace amines, amphetamines, ergoline derivatives, adrenergic ligands, and catecholamine metabolites, suggesting a novel intercellular signaling system and a potential additional mechanism for amphetamine effects. |
Abstract
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.