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Determinants involved in subtype-specific functions of rat trace amine-associated receptors 1 and 4.

ABSTRACT: AIMS:The trace amine-associated receptor (Taar) family displays high species- and subtype-specific pharmacology. Several trace amines such as ?-phenylethylamine (?-PEA), p-tyramine and tryptamine are agonists at TA(1) but poorly activate rat and mouse Taar4. PRINCIPAL RESULTS:Using rat TA(1) and Taar4 chimera, we identified determinants in transmembrane helices 3 and 6, which, when replaced by the corresponding portion of rat TA(1) , can rescue cell surface expression of rat Taar4. When expressed at the cell surface, rat Taar4 pharmacology was very similar to that of TA(1) and coupled to the G?(s) -protein/AC pathway. Our data suggest that binding pockets of Taar for surrogate agonists overlap between paralogs. CONCLUSIONS:This implicates that the repertoire of Taar ensures functional redundancy, tissue- and cell-specific expression and/or different downstream signalling rather than different agonist specificity.

SUBMITTER: Staubert C

PROVIDER: S-EPMC3594682 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Determinants involved in subtype-specific functions of rat trace amine-associated receptors 1 and 4.

Stäubert C C Bohnekamp J J Schöneberg T T

British journal of pharmacology 20130301 5

<h4>Aims</h4>The trace amine-associated receptor (Taar) family displays high species- and subtype-specific pharmacology. Several trace amines such as β-phenylethylamine (β-PEA), p-tyramine and tryptamine are agonists at TA(1) but poorly activate rat and mouse Taar4.<h4>Principal results</h4>Using rat TA(1) and Taar4 chimera, we identified determinants in transmembrane helices 3 and 6, which, when replaced by the corresponding portion of rat TA(1) , can rescue cell surface expression of rat Taa ...[more]

PMID: 23072560

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