Dopamine interacts directly with its D3 and D2 receptors on normal human T cells, and activates β1 integrin function

M. Levite*, Y. Chowers, Y. Ganor, M. Besser, R. Hershkovits, L. Cahalon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Dopamine by itself has not up to now been reported to activate T cell function. We show here that dopamine interacts directly with dopaminergic receptors on normal human T cells and triggers β1 integrin-mediated T cell adhesion to a major extracellular matrix component, fibronectin (FN). Such adhesion is a characteristic feature of activated T cells, and is critical for trafficking and extravasation of T cells across blood vessels and tissue barriers. Seven dopamine D2/D3 receptor agonists and antagonists were used to identify the receptor subtypes with which dopamine specifically interacts to activate T cells. The D3 dopamine receptor agonist, 7-hydroxy-DPAT (DPAT), mimics the effects of dopamine, and the effects of both dopamine and DPAT are blocked by a specific D3 receptor antagonist, U-maleate. The dopamine receptor agonists bromocriptine and pergolide mimic the direct effect of dopamine on the β1 integrin function, while the dopamine receptor antagonists butaclamol and haloperidol suppress it, suggesting additional signaling via the dopamine D2 receptor subtype. Our study shows, for the first time, that dopamine can directly activate T cells via its specific receptors and suggests a possible role for dopamine in integrin-mediated cellular trafficking and extravasation of T cells in the central nervous system and possibly also in the periphery. Finally, we suggest that the reported changes in the D3 and D2 receptor RNA levels in peripheral blood lymphocytes of individuals with schizophrenia, Parkinson's disease, Alzheimer's disease and migraine can serve not only as a 'passive' diagnostic marker, but primarily reflect the dynamic functional dopamine-T cell interactions in these diseases.

Original languageEnglish
Pages (from-to)3504-3512
Number of pages9
JournalEuropean Journal of Immunology
Volume31
Issue number12
DOIs
StatePublished - 2001

Keywords

  • D3, D2 receptors
  • Dopamine
  • Neuroimmunomodulation
  • T cell adhesion
  • β1 integrin

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