British Journal of Pharmacology 2013-03-01

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

C Stäubert, J Bohnekamp, T Schöneberg

Index: Br. J. Pharmacol. 168(5) , 1266-78, (2013)

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Abstract

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.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.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.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.