Vonk Argo, Reinart Reet, Rinken Ago
Institute of Chemistry, University of Tartu, Jakobi 2, Tartu, Estonia.
J Pharmacol Sci. 2008 Sep;108(1):63-70. doi: 10.1254/jphs.08019fp.
We have characterized the modulation of adenylyl cyclase (AC) activity by ligands of dopaminergic receptors in rat striatal homogenate and compared the results with receptor-ligand binding affinities. Despite the fact that rat striatum contains high level of both dopamine D(1) and D(2) receptors, only the D(1)-specific AC activation by agonists could be determined. All D(1)-receptor agonists (dopamine, dihydrexidine, and A 77636) used were able to increase cAMP accumulation in a concentration-dependent manner, while D(1)-receptor antagonists (SCH23390, SKF83566, and butaclamol) blocked the effects induced by the aforementioned agonists. At the same time, the D(2)-receptor agonist quinpirole and antagonist sulpiride had no effect on cAMP accumulation in striatal homogenate neither on the basal level nor on the activated level of AC, while inhibited [(3)H]raclopride binding to these membranes. Comparing the ligands of the D(1) receptor in modulating the activity of AC and displacing D(1)-receptor-specific radioligand [(3)H]SCH23390 binding revealed that the ligands modulate both of these processes with similar affinities. It indicates that under given experimental conditions, only dopamine D(1)-receptor-mediated stimulation of AC activity can be measured in membrane homogenate of rat striatum, while dopamine D(2)-receptor effects remain fully hidden.
我们已对大鼠纹状体匀浆中多巴胺能受体配体对腺苷酸环化酶（AC）活性的调节进行了表征，并将结果与受体 - 配体结合亲和力进行了比较。尽管大鼠纹状体中多巴胺D(1)和D(2)受体含量都很高，但仅能确定激动剂对D(1)特异性的AC激活作用。所有使用的D(1)受体激动剂（多巴胺、二氢麦角隐亭和A 77636）均能以浓度依赖的方式增加cAMP积累，而D(1)受体拮抗剂（SCH23390、SKF83566和布他拉莫）则阻断上述激动剂诱导的效应。同时，D(2)受体激动剂喹吡罗和拮抗剂舒必利对纹状体匀浆中cAMP积累在基础水平和AC激活水平均无影响，却能抑制[(3)H]雷氯必利与这些膜的结合。比较D(1)受体配体在调节AC活性和取代D(1)受体特异性放射性配体[(3)H]SCH23390结合方面的作用发现，这些配体以相似的亲和力调节这两个过程。这表明在给定的实验条件下，在大鼠纹状体膜匀浆中仅能检测到多巴胺D(1)受体介导的AC活性刺激，而多巴胺D(2)受体的效应则完全隐藏。
