Research article summary (published 21 Oct 2009):

Human and mouse trace amine-associated receptor 1 have distinct pharmacology towards endogenous monoamines and imidazoline receptor ligands.

Full Abstract

TAARs (trace amine-associated receptors) are G-protein-coupled receptors that respond to low abundance, endogenous amines such as tyramine and tryptamine, and represent potential targets for neuropsychiatric diseases. However, some members of this receptor subfamily either have no ligand identified or remain difficult to express and characterize using recombinant systems. In the present paper we report the successful expression of human and mouse TAAR1, and the characterization of their responses to various natural and synthetic agonists. In HEK (human embryonic kidney)-293/CRE-bla cells, mouse TAAR1 showed a robust response to trace amines as measured using either a cAMP assay or a beta-lactamase reporter assay, whereas human TAAR1 showed a weaker, but still measurable, response. When certain fragments of human TAAR1 were replaced with the corresponding regions of mouse TAAR1, the chimaeric receptor showed a much stronger response in cAMP production. Examination of a series of agonists on these receptors revealed that the human and the chimaeric receptor are almost identical in pharmacology, but distinct from the mouse receptor. We also screened small libraries of pharmacologically active agents on TAAR1 and identified a series of synthetic agonists, some of which are also ligands of the enigmatic imidazoline receptor. The findings of the present study not only shed light on the pharmacological species difference of TAAR1, but also raise new possibilities about the mechanism of some of the imidazoline-related agents.

Author information

Author/s: Hu, Liaoyuan A (LA); Zhou, Tian (T); Ahn, Jinwoo (J); Wang, Shuli (S); Zhou, Julia (J); Hu, Yi (Y); Liu, Qingyun (Q);

Affiliation: Department of Pharmaceutical Discovery, Lexicon Pharmaceuticals, Inc., 8800 Technology Forest Place, The Woodlands, TX 77381, USA. lhu(-atsign-)lexpharma.com

Journal and publication information

Publication Type: Journal Article

Journal: The Biochemical journal (Biochem J), published in England. (Language: eng)

Reference: 2009-Nov; vol 424 (issue 1) : pp 39-45

Dates: Created 2009/10/20; Completed 2009/11/03;

PMID: 19725810, status: MEDLINE (last retrieval date: 11/3/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adrenergic Uptake Inhibitors - pharmacology Animals COS Cells Cell Line Central Nervous System Stimulants - pharmacology Cercopithecus aethiops Cyclic AMP - metabolism Humans Imidazoline Receptors - agonists; metabolism

Mice Octopamine - pharmacology Phenethylamines - pharmacology Psychotropic Drugs - pharmacology Receptors, G-Protein-Coupled - agonists; genetics; metabolism Recombinant Fusion Proteins - agonists; genetics; metabolism Synephrine - pharmacology Tryptamines - pharmacology Tyramine - pharmacology

Associated Chemicals: Adrenergic Uptake Inhibitors (0) ; Central Nervous System Stimulants (0) ; Imidazoline Receptors (0) ; Phenethylamines (0) ; Psychotropic Drugs (0) ; Receptors, G-Protein-Coupled (0) ; Recombinant Fusion Proteins (0) ; Trace amine-associated receptor 1 (0) ; Tryptamines (0) ; Octopamine (104-14-3) ; Tyramine (51-67-2) ; Cyclic AMP (60-92-4) ; tryptamine (61-54-1) ; phenethylamine (64-04-0) ; Synephrine (94-07-5)

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