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

J. R. Bunzow, M. S. Sonders, Seksiri Arttamangkul, L. M. Harrison, G. Zhang, D. I. Quigley, T. Darland, K. L. Suchland, S. Pasumamula, J. L. Kennedy, Susan Olson, R. E. Magenis, S. G. Amara, David Grandy

Research output: Contribution to journalArticle

368 Citations (Scopus)

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, β-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.

Original languageEnglish (US)
Pages (from-to)1181-1188
Number of pages8
JournalMolecular Pharmacology
Volume60
Issue number6
StatePublished - 2001

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Amphetamines
N-Methyl-3,4-methylenedioxyamphetamine
Lysergic Acid Diethylamide
Amphetamine
Tyramine
Catecholamines
Amines
Neurotransmitter Agents
Ergolines
Neurotransmitter Transport Proteins
Pharmacology
Octopamine
Ligands
Biogenic Amines
G-Protein-Coupled Receptors
Adrenergic Agents
Vertebrates
Brain
Pharmaceutical Preparations
Trace amine-associated receptor 1

ASJC Scopus subject areas

  • Pharmacology

Cite this

Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. / Bunzow, J. R.; Sonders, M. S.; Arttamangkul, Seksiri; Harrison, L. M.; Zhang, G.; Quigley, D. I.; Darland, T.; Suchland, K. L.; Pasumamula, S.; Kennedy, J. L.; Olson, Susan; Magenis, R. E.; Amara, S. G.; Grandy, David.

In: Molecular Pharmacology, Vol. 60, No. 6, 2001, p. 1181-1188.

Research output: Contribution to journalArticle

Bunzow, JR, Sonders, MS, Arttamangkul, S, Harrison, LM, Zhang, G, Quigley, DI, Darland, T, Suchland, KL, Pasumamula, S, Kennedy, JL, Olson, S, Magenis, RE, Amara, SG & Grandy, D 2001, 'Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor', Molecular Pharmacology, vol. 60, no. 6, pp. 1181-1188.
Bunzow, J. R. ; Sonders, M. S. ; Arttamangkul, Seksiri ; Harrison, L. M. ; Zhang, G. ; Quigley, D. I. ; Darland, T. ; Suchland, K. L. ; Pasumamula, S. ; Kennedy, J. L. ; Olson, Susan ; Magenis, R. E. ; Amara, S. G. ; Grandy, David. / Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. In: Molecular Pharmacology. 2001 ; Vol. 60, No. 6. pp. 1181-1188.
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