Cao Yan, Sun Wan-Chun, Jin Lei, Xie Ke-Qiang, Zhu Xing-Zu
Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Eur J Pharmacol. 2006 Oct 24;548(1-3):29-35. doi: 10.1016/j.ejphar.2006.07.051. Epub 2006 Aug 3.
The antagonistic interactions between adenosine A1 receptors and dopamine D1 receptors were studied in a human embryonic kidney 293 cell line stably cotransfected with human adenosine A1 receptor and dopamine D1 receptor cDNAs. In the cotransfected cells, but not in control cells only transfected with dopamine D1 receptors, adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA, 10 microM) increased the Kd of dopamine D1 receptor antagonist [N-methyl-3H]R(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine ([3H]SCH23390) without affecting the Bmax. Moreover, CPA induced a concentration-dependent decrease in the affinity of dopamine D1 receptors for the agonist (+/-)-1-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF38393) and inhibited dopamine D1 receptor-mediated cyclic AMP response element recruitment. Furthermore, pertussis toxin treatment completely counteracted the effects of low concentrations of CPA but only partially counteracted the effects of high concentrations of CPA. These results suggest that adenosine A1 receptors antagonistically modulate dopamine D1 receptors at the level of receptor binding and the second messenger generation. Furthermore, the antagonistic interactions between these two receptors induced by low concentrations of CPA might have a different manner with those induced by high concentrations of CPA.
在稳定共转染人腺苷A1受体和多巴胺D1受体cDNA的人胚肾293细胞系中研究了腺苷A1受体与多巴胺D1受体之间的拮抗相互作用。在共转染的细胞中，而非仅转染多巴胺D1受体的对照细胞中，腺苷A1受体激动剂N6-环戊基腺苷（CPA，10微摩尔）增加了多巴胺D1受体拮抗剂[N-甲基-3H]R(+)-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓（[3H]SCH23390）的解离常数（Kd），而不影响最大结合容量（Bmax）。此外，CPA诱导多巴胺D1受体对激动剂(+/-)-1-苯基-2,3,4,5-四氢-(1H)-3-苯并氮杂卓-7,8-二醇盐酸盐（SKF38393）的亲和力呈浓度依赖性降低，并抑制多巴胺D1受体介导的环磷酸腺苷反应元件募集。此外，百日咳毒素处理完全抵消了低浓度CPA的作用，但仅部分抵消了高浓度CPA的作用。这些结果表明，腺苷A1受体在受体结合和第二信使生成水平上对多巴胺D1受体进行拮抗调节。此外，低浓度CPA诱导的这两种受体之间的拮抗相互作用可能与高浓度CPA诱导的相互作用方式不同。
