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

Br J Pharmacol. 2013 Mar;168(5):1266-78. doi: 10.1111/bph.12020.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Membrane / metabolism
  • Chlorocebus aethiops
  • HEK293 Cells
  • Humans
  • Phenethylamines / pharmacology
  • Protein Transport
  • Rats
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Tryptamines / pharmacology
  • Tyramine / pharmacology


  • Phenethylamines
  • Receptors, G-Protein-Coupled
  • TAAR4 protein, rat
  • Tryptamines
  • phenethylamine
  • tryptamine
  • Tyramine
  • Trace amine-associated receptor 1