RESUMEN
AIMS: The trace amine-associated receptor (Taar) family displays high species- and subtype-specific pharmacology. Several trace amines such as ß-phenylethylamine (ß-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.