Trace amine-associated receptors and their ligands

R. Zucchi, G. Chiellini, Thomas (Tom) Scanlan, David Grandy

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    182 Scopus citations

    Abstract

    Classical biogenic amines (adrenaline, noradrenaline, dopamine, serotonin and histamine) interact with specific families of G protein-coupled receptors (GPCRs). The term 'trace amines' is used when referring to p-tyramine, Β-phenylethylamine, tryptamine and octopamine, compounds that are present in mammalian tissues at very low (nanomolar) concentrations. The pharmacological effects of trace amines are usually attributed to their interference with the aminergic pathways, but in 2001 a new gene was identified, that codes for a GPCR responding to p-tyramine and Β-phenylethylamine but not to classical biogenic amines. Several closely related genes were subsequently identified and designated as the trace amine-associated receptors (TAARs). Pharmacological investigations in vitro show that many TAAR subtypes may not respond to p-tyramine, Β-phenylethylamine, tryptamine or octopamine, suggesting the existence of additional endogenous ligands. A novel endogenous thyroid hormone derivative, 3-iodothyronamine, has been found to interact with TAAR1 and possibly other TAAR subtypes. In vivo, micromolar concentrations of 3-iodothyronamine determine functional effects which are opposite to those produced on a longer time scale by thyroid hormones, including reduction in body temperature and decrease in cardiac contractility. Expression of all TAAR subtypes except TAAR1 has been reported in mouse olfactory epithelium, and several volatile amines were shown to interact with specific TAAR subtypes. In addition, there is evidence that TAAR1 is targeted by amphetamines and other psychotropic agents, while genetic linkage studies show a significant association between the TAAR gene family locus and susceptibility to schizophrenia or bipolar affective disorder.

    Original languageEnglish (US)
    Pages (from-to)967-978
    Number of pages12
    JournalBritish Journal of Pharmacology
    Volume149
    Issue number8
    DOIs
    Publication statusPublished - Dec 30 2006

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    Keywords

    • Amphetamine
    • G-protein coupled receptors
    • Signal transduction
    • Thyroid hormone
    • Thyronamines
    • Trace amines
    • Tyramine

    ASJC Scopus subject areas

    • Pharmacology

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