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


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.
Institute of Biochemistry, Medical Faculty, University Leipzig, Leipzig, Germany.
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Stäubert
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Bohnekamp
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Schöneberg
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D010627:Phenethylamines / Q000494:pharmacology; D021381:Protein Transport; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014363:Tryptamines / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology; D000095383:Trace Amine-Associated Receptors
D010627:Phenethylamines; D043562:Receptors, G-Protein-Coupled; D014363:Tryptamines; D014439:Tyramine; D000095383:Trace Amine-Associated Receptors; C582779:TAAR4 protein, rat; C029261:phenethylamine; C030820:tryptamine