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• W2080845065 abstract "Adenosine A(2A) receptors (A(2A)Rs) and dopamine D(2) receptors (D(2)Rs) form constitutive heteromers in living cells and exhibit a strong functional antagonistic interaction. Recent findings give neurochemical evidence that extended cocaine self-administration in the rat give rise to an up-regulation of functional A(2A)Rs in the nucleus accumbens that return to baseline expression levels during cocaine withdrawal. In the present work, the acute in vitro effects of a concentration of cocaine known to fully block the dopamine (DA) transporter without exerting any toxic actions were investigated on A(2A)R and D(2L)R formed heteromers in transiently co-transfected HEK-293T cells. In vitro treatment of cocaine was found to produce changes in D(2)R homodimers and in A(2A)R-D(2)R heterodimers detected through bioluminescent energy transfer (BRET). Cocaine was found to produce a time- and concentration-dependent reduction in the BRET(max) between A(2A)R-D(2L)R heterodimers and D(2L)R homodimers, but not A(2A)R homodimers, indicating its effect on D(2)R. Cocaine was evaluated with regard to D(2)R binding using a human D(2L)R stable expressing CHO cell line and was found to produce an increase in the affinity of hD(2L)R for DA. At the level of G protein-coupling, cocaine produced a small, but significant increase in DA-stimulated binding of GTPgammaS. However, cocaine failed to modulate D(2)R agonist-induced inhibition of cAMP in stable hD(2L)R CHO cells or the gating of GIRK channels in oocytes. Taken together, these results indicate a direct and specific effect of a moderate concentration of cocaine on the DA D(2L)R, that results in enhanced agonist recognition, G protein-coupling and an altered conformational state of D(2)R homodimers and A(2A)R-D(2)R heterodimers." @default.
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• W2080845065 date "2010-04-01" @default.
• W2080845065 modified "2023-10-01" @default.
• W2080845065 title "Cocaine produces D2R-mediated conformational changes in the adenosine A2AR-dopamine D2R heteromer" @default.
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• W2080845065 doi "https://doi.org/10.1016/j.bbrc.2010.03.104" @default.
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