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

作者：Staeubert C; Bohnekamp J; Schoeneberg T^*

来源：British Journal of Pharmacology, 2013, 168(5): 1266-1278.

DOI：10.1111/bph.12020

• Taar
• trace amine-associated receptor
• GPCR

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 TA1 but poorly activate rat and mouse Taar4. Principal Results Using rat TA1 and Taar4 chimera, we identified determinants in transmembrane helices 3 and 6, which, when replaced by the corresponding portion of rat TA1, can rescue cell surface expression of rat Taar4. When expressed at the cell surface, rat Taar4 pharmacology was very similar to that of TA1 and coupled to the Gs-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.

• 出版日期2013-3