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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 β-phenylethylamine (β-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 Gα(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.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Stäubert C,Bohnekamp J,Schöneberg T

doi

10.1111/bph.12020

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

1266-78

issue

5

eissn

0007-1188

issn

1476-5381

journal_volume

168

pub_type

杂志文章

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