title: Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2.
abstract: Certain biogenic amines, such as 2-PEA, TYR, or T1AM, modulate blood pressure, cardiac function, brain monoaminergic systems, and olfaction-guided behavior by specifically interacting with members of a group of rhodopsin-like receptors, TAAR. A receptor that is absent from olfactory epithelia but had long been identified in the brain and a variety of peripheral tissues, TAAR1 has been found recently in blood B cells, suggesting a functional role of TAAR1 in these cells. With the present study, we have set out to clarify the expression and functional roles of TAAR in different isolated human blood leukocyte types. Here, we report the functional expression of TAAR1 and its closest relative TAAR2 in blood PMN and T and B cells. Both receptors are coexpressed in a subpopulation of PMN, where they are necessary for the chemosensory migration toward the TAAR1 ligands 2-PEA, TYR, and T1AM, with EC50 values of 0.43 ± 0.05 nM, 0.52 ± 0.05 nM, and 0.25 ± 0.04 nM, respectively. The same amines, with similar potencies, triggered cytokine or Ig secretion, in purified blood T or B cells, respectively. Notably, 2-PEA regulated mRNA expression of 28 T cell function-related genes, above all of the CCL5. In siRNA-guided experiments, TAAR1 and TAAR2 proved to be necessary for amine-induced blood leukocyte functions. In summary, our results demonstrate that biogenic amines potently regulate blood cell functions via TAAR1 and TAAR2 and open the perspective of their specific pharmacological modulation.
authors: German Research Center for Food Chemistry Leibniz Institute, Physiology, Lise-Meitner-Strasse 34, Freising, Germany.
authors: Agne
authors: A
authors: Babusyte
authors: Matthias
authors: M
authors: Kotthoff
authors: Julia
authors: J
authors: Fiedler
authors: Dietmar
authors: D
authors: Krautwurst
mesh_terms: D000906:Antibodies / Q000276:immunology; D001679:Biogenic Amines / Q000276:immunology / Q000494:pharmacology*; D018946:Chemokine CCL5 / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D008297:Male; D043562:Receptors, G-Protein-Coupled / Q000276:immunology*; D000095383:Trace Amine-Associated Receptors
chemical_list: D000906:Antibodies; D001679:Biogenic Amines; D018946:Chemokine CCL5; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors; C483024:CCL5 protein, human; C408786:TAAR2 protein, human