Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2
Abstract
TAAR1 and TAAR2 are necessary for biogenic amine-induced in vitro activation of PMN migration, Th-cell cytokine secretion, and B-cell immunoglobulin E production. 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.
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TAAR1 activation leads to intracellular cAMP signalling that results in PKA and PKC phosphorylation and activation.
“TAAR1 activation leads to intracellular cAMP signalling that results in PKA and PKC phosphorylation and activation [178–180].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [178]
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- Authors
- Babusyte, A., Kotthoff, M., Fiedler, J., & Krautwurst, D.
- Affiliations
- German Research Center for Food Chemistry Leibniz Institute , Physiology, Freising, Germany
- Leibniz-Institute for Food Systems Biology at the Technical University of Munich (DE)
- Corresponding author
- Krautwurst, Dietmar
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-01-11
- Volume
- 93
- Issue
- 3
- Pages
- 387-394
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2109347290
- Cited by
- 146
- References
- 42
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 8 · 2023: 8 · 2022: 15 · 2021: 15 · 2020: 4 · 2019: 15 · 2018: 13 · 2017: 10 · 2016: 18 · 2015: 8 · 2014: 6 · 2013: 1
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- German Academic Exchange Service
- Fonds der Chemischen Industrie (FCI)-Kékulé (K184/16)
- International Foundation for the Promotion of Nutrition Research and Nutrition Education
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Keywords
- trace amine-associated receptors, TAAR1, biogenic amines, leukocyte activation, neutrophils, T cells, B cells, tyramine, chemotaxis, cytokine production, RANTES, rhodopsin-like receptors, blood leukocytes
- MeSH terms
- Trace Amine-Associated Receptors, Antibodies, Biogenic Amines, Dose-Response Relationship, Drug, Female, Humans, Leukocytes, Mononuclear, Male, Chemokine CCL5, Receptors, G-Protein-Coupled
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