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Dopamine interacts directly with its D3 and D2 receptors on normal human T cells, and activates beta1 integrin function.

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 beta1 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 beta1 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 ist 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.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

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

doi

10.1002/1521-4141(200112)31:12<3504::aid-immu3504>

keywords:

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

3504-12

issue

eissn

0014-2980

issn

1521-4141

pii

10.1002/1521-4141(200112)31:12<3504::AID-IMMU3504>

journal_volume

pub_type

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Dopamine interacts directly with its D3 and D2 receptors on normal human T cells, and activates beta1 integrin function.