The enhancement of dopamine D1 receptor desensitization by adenosine A1 receptor activation

The present study was designed to examine the effects of adenosine A1 receptor on dopamine D1 receptor desensitization in a human embryonic kidney 293 cell line stably cotransfected with human adenosine A1 receptor and dopamine D1 receptor cDNAs (A1D1 cells) by means of cAMP accumulation assay. Long-term exposure of A1D1 cells to dopamine D1 receptor agonist (±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF38393) caused a rapid desensitization of dopamine D1 receptor. Coadministration of adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) potentiated the effect of SKF38393. This enhancement effect of CPA was blocked by adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) but not by pertussis toxin, indicating that this effect of CPA was mediated by adenosine A1 receptor and was Gi protein independent. Furthermore, the blockade of endogenous adenosine by adenosine deaminase or DPCPX attenuated dopamine D1 receptor desensitization. Collectively, these results suggest that adenosine A1 receptor plays an important role in the regulation of dopamine D1 receptor by potentiating ligand-induced desensitization.