Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and Para-hydroxyamphetamine

E. A. Reese, J. R. Bunzow, Seksiri Arttamangkul, M. S. Sonders, David Grandy

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

The synthetic amines methamphetamine (METH), amphetamine (AMPH), and their metabolite para-hydroxyamphetamine (POHA) are chemically and structurally related to the catecholamine neurotransmitters and a small group of endogenous biogenic amines collectively referred to as the trace amines (TAs). Recently, it was reported that METH, AMPH, POHA, and the TAs para-tyramine (TYR) and β-phenylethylamine (PEA) stimulate cAMP production in human embryonic kidney (HEK)-293 cells expressing rat trace amine-associated receptor 1 (rTAAR1). The discovery that METH and AMPH activate the rTAAR1 motivated us to study the effect of these drugs on the mouse TAAR1 (mTAAR1) and a human-rat chimera (h-rChTAAR1). Furthermore, because S-(+)-isomers of METH and AMPH are reported to be more potent and efficacious in vivo than R-(-), we determined the enantiomeric selectivity of all three species of TAAR1. In response to METH, AMPH, or POHA exposure, the accumulation of cAMP by HEK-293 cells stably expressing different species of TAAR1 was concentration- and isomer-dependent. EC50 values for S-(+)-METH were 0.89, 0.92, and 4.44 μM for rTAAR1, mTAAR1, and h-rChTAAR1, respectively. PEA was a potent and full agonist at each species of TAAR1, whereas TYR was a full agonist for the rodent TAAR1s but was a partial agonist at h-rChTAAR1. Interestingly, both isomers of METH were full agonists at mTAAR1 and h-rChTAAR1, whereas both were partial agonists at rTAAR1. Taken together, these in vitro results suggest that, in vivo, TAAR1 could be a novel mediator of the effects of these drugs.

Original languageEnglish (US)
Pages (from-to)178-186
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume321
Issue number1
DOIs
StatePublished - Apr 2007

Fingerprint

p-Hydroxyamphetamine
Methamphetamine
Amphetamine
Amines
Phenethylamines
Tyramine
Kidney
Biogenic Amines
Trace amine-associated receptor 1
Pharmaceutical Preparations
Catecholamines
Neurotransmitter Agents
Rodentia

ASJC Scopus subject areas

  • Pharmacology

Cite this

Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and Para-hydroxyamphetamine. / Reese, E. A.; Bunzow, J. R.; Arttamangkul, Seksiri; Sonders, M. S.; Grandy, David.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 321, No. 1, 04.2007, p. 178-186.

Research output: Contribution to journalArticle

@article{ed1f1aa2338241f8a1c19166756c09bd,
title = "Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and Para-hydroxyamphetamine",
abstract = "The synthetic amines methamphetamine (METH), amphetamine (AMPH), and their metabolite para-hydroxyamphetamine (POHA) are chemically and structurally related to the catecholamine neurotransmitters and a small group of endogenous biogenic amines collectively referred to as the trace amines (TAs). Recently, it was reported that METH, AMPH, POHA, and the TAs para-tyramine (TYR) and β-phenylethylamine (PEA) stimulate cAMP production in human embryonic kidney (HEK)-293 cells expressing rat trace amine-associated receptor 1 (rTAAR1). The discovery that METH and AMPH activate the rTAAR1 motivated us to study the effect of these drugs on the mouse TAAR1 (mTAAR1) and a human-rat chimera (h-rChTAAR1). Furthermore, because S-(+)-isomers of METH and AMPH are reported to be more potent and efficacious in vivo than R-(-), we determined the enantiomeric selectivity of all three species of TAAR1. In response to METH, AMPH, or POHA exposure, the accumulation of cAMP by HEK-293 cells stably expressing different species of TAAR1 was concentration- and isomer-dependent. EC50 values for S-(+)-METH were 0.89, 0.92, and 4.44 μM for rTAAR1, mTAAR1, and h-rChTAAR1, respectively. PEA was a potent and full agonist at each species of TAAR1, whereas TYR was a full agonist for the rodent TAAR1s but was a partial agonist at h-rChTAAR1. Interestingly, both isomers of METH were full agonists at mTAAR1 and h-rChTAAR1, whereas both were partial agonists at rTAAR1. Taken together, these in vitro results suggest that, in vivo, TAAR1 could be a novel mediator of the effects of these drugs.",
author = "Reese, {E. A.} and Bunzow, {J. R.} and Seksiri Arttamangkul and Sonders, {M. S.} and David Grandy",
year = "2007",
month = "4",
doi = "10.1124/jpet.106.115402",
language = "English (US)",
volume = "321",
pages = "178--186",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

TY - JOUR

T1 - Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and Para-hydroxyamphetamine

AU - Reese, E. A.

AU - Bunzow, J. R.

AU - Arttamangkul, Seksiri

AU - Sonders, M. S.

AU - Grandy, David

PY - 2007/4

Y1 - 2007/4

N2 - The synthetic amines methamphetamine (METH), amphetamine (AMPH), and their metabolite para-hydroxyamphetamine (POHA) are chemically and structurally related to the catecholamine neurotransmitters and a small group of endogenous biogenic amines collectively referred to as the trace amines (TAs). Recently, it was reported that METH, AMPH, POHA, and the TAs para-tyramine (TYR) and β-phenylethylamine (PEA) stimulate cAMP production in human embryonic kidney (HEK)-293 cells expressing rat trace amine-associated receptor 1 (rTAAR1). The discovery that METH and AMPH activate the rTAAR1 motivated us to study the effect of these drugs on the mouse TAAR1 (mTAAR1) and a human-rat chimera (h-rChTAAR1). Furthermore, because S-(+)-isomers of METH and AMPH are reported to be more potent and efficacious in vivo than R-(-), we determined the enantiomeric selectivity of all three species of TAAR1. In response to METH, AMPH, or POHA exposure, the accumulation of cAMP by HEK-293 cells stably expressing different species of TAAR1 was concentration- and isomer-dependent. EC50 values for S-(+)-METH were 0.89, 0.92, and 4.44 μM for rTAAR1, mTAAR1, and h-rChTAAR1, respectively. PEA was a potent and full agonist at each species of TAAR1, whereas TYR was a full agonist for the rodent TAAR1s but was a partial agonist at h-rChTAAR1. Interestingly, both isomers of METH were full agonists at mTAAR1 and h-rChTAAR1, whereas both were partial agonists at rTAAR1. Taken together, these in vitro results suggest that, in vivo, TAAR1 could be a novel mediator of the effects of these drugs.

AB - The synthetic amines methamphetamine (METH), amphetamine (AMPH), and their metabolite para-hydroxyamphetamine (POHA) are chemically and structurally related to the catecholamine neurotransmitters and a small group of endogenous biogenic amines collectively referred to as the trace amines (TAs). Recently, it was reported that METH, AMPH, POHA, and the TAs para-tyramine (TYR) and β-phenylethylamine (PEA) stimulate cAMP production in human embryonic kidney (HEK)-293 cells expressing rat trace amine-associated receptor 1 (rTAAR1). The discovery that METH and AMPH activate the rTAAR1 motivated us to study the effect of these drugs on the mouse TAAR1 (mTAAR1) and a human-rat chimera (h-rChTAAR1). Furthermore, because S-(+)-isomers of METH and AMPH are reported to be more potent and efficacious in vivo than R-(-), we determined the enantiomeric selectivity of all three species of TAAR1. In response to METH, AMPH, or POHA exposure, the accumulation of cAMP by HEK-293 cells stably expressing different species of TAAR1 was concentration- and isomer-dependent. EC50 values for S-(+)-METH were 0.89, 0.92, and 4.44 μM for rTAAR1, mTAAR1, and h-rChTAAR1, respectively. PEA was a potent and full agonist at each species of TAAR1, whereas TYR was a full agonist for the rodent TAAR1s but was a partial agonist at h-rChTAAR1. Interestingly, both isomers of METH were full agonists at mTAAR1 and h-rChTAAR1, whereas both were partial agonists at rTAAR1. Taken together, these in vitro results suggest that, in vivo, TAAR1 could be a novel mediator of the effects of these drugs.

UR - http://www.scopus.com/inward/record.url?scp=33947416920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947416920&partnerID=8YFLogxK

U2 - 10.1124/jpet.106.115402

DO - 10.1124/jpet.106.115402

M3 - Article

VL - 321

SP - 178

EP - 186

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 1

ER -