TY - JOUR
T1 - Dopamine interacts directly with its D3 and D2 receptors on normal human T cells, and activates β1 integrin function
AU - Levite, M.
AU - Chowers, Y.
AU - Ganor, Y.
AU - Besser, M.
AU - Hershkovits, R.
AU - Cahalon, L.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - β1 integrin
KW - D3, D2 receptors
KW - Dopamine
KW - Neuroimmunomodulation
KW - T cell adhesion
UR - http://www.scopus.com/inward/record.url?scp=0035668526&partnerID=8YFLogxK
U2 - 10.1002/1521-4141(200112)31:12<3504::AID-IMMU3504>3.0.CO;2-F
DO - 10.1002/1521-4141(200112)31:12<3504::AID-IMMU3504>3.0.CO;2-F
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C2 - 11745370
AN - SCOPUS:0035668526
SN - 0014-2980
VL - 31
SP - 3504
EP - 3512
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -