The enhancement of dopamine D1 receptor desensitization by adenosine A1 receptor activation.
The present study was designed to examine the effects of adenosine A(1) receptor on dopamine D(1) receptor desensitization in a human embryonic kidney 293 cell line stably cotransfected with human adenosine A(1) receptor and dopamine D(1) receptor cDNAs (A(1)D(1) cells) by means of cAMP accumulation assay. Long-term exposure of A(1)D(1) cells to dopamine D(1) receptor agonist (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF38393) caused a rapid desensitization of dopamine D(1) receptor. Coadministration of adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA) potentiated the effect of SKF38393. This enhancement effect of CPA was blocked by adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) but not by pertussis toxin, indicating that this effect of CPA was mediated by adenosine A(1) receptor and was G(i) protein independent. Furthermore, the blockade of endogenous adenosine by adenosine deaminase or DPCPX attenuated dopamine D(1) receptor desensitization. Collectively, these results suggest that adenosine A(1) receptor plays an important role in the regulation of dopamine D(1) receptor by potentiating ligand-induced desensitization.
Cao
Yan
Y
Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China. ycao@sibs.ac.cn
Xie
Ke-Qiang
KQ
Zhu
Xing-Zu
XZ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D001667:Binding, Competitive; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014162:Transfection; D014970:Xanthines / Q000494:pharmacology
D018491:Dopamine Agonists; D043682:Receptor, Adenosine A1; D017447:Receptors, Dopamine D1; D014970:Xanthines; C048599:N(6)-cyclopentyladenosine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D000241:Adenosine