Actions of dopamine and dopaminergic drugs on cloned serotonin receptors expressed in Xenopus oocytes.
Actions of dopamine and dopaminergic drugs on cloned serotonin receptors expressed in Xenopus oocytes.
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DOI：
10.1073/pnas.89.10.4708
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发表时间：
1992-05
影响因子：
11.1
通讯作者：
R. Woodward;M. Panicker;R. Miledi
中科院分区：
文献类型：
--
作者：
R. Woodward;M. Panicker;R. Miledi
使用电生理技术，我们研究了多巴胺和选择多巴胺能药物与5-羟色胺（5-HT）受体表达的非洲爪蟾卵母细胞从克隆cDNA转录的RNA的相互作用。显示5-HT 1c和5-HT 2受体强表达的卵母细胞对神经递质多巴胺的反应变弱，多巴胺和5-HT一样，通过激活磷脂酰肌醇/Ca 2+信使途径引起Cl-电流。两种类型的5-HT受体对多巴胺表现出相似的敏感性;阈值反应在低至1 μ M的浓度下被激活。然而，最大多巴胺反应仅为5-HT激活的最大反应的5-20%。多巴胺D1受体拮抗剂SCH 23390是5-HT 1c和5-HT 2受体的强效激动剂。SCH 23390在低至1 nM的浓度下引发电流，但最大反应也仅为5-HT激活的反应的5-20%。多巴胺D1受体激动剂非诺多泮也与5-HT 1c和5-HT 2受体相互作用，引发10至20 nM的阈值反应。我们的实验提高了这样的可能性，即低微摩尔浓度的多巴胺可以导致弱激活和伴随的脱敏的体内多巴胺能系统，并证明苯并氮杂卓可以相互作用与5-HT受体在纳摩尔浓度。
Using electrophysiological techniques, we studied interactions of dopamine and selected dopaminergic drugs with serotonin (5-hydroxytryptamine; 5-HT) receptors expressed in Xenopus oocytes by RNAs transcribed from cloned cDNAs. Oocytes showing strong expression of 5-HT1c and 5-HT2 receptors became weakly responsive to the neurotransmitter dopamine, which, like 5-HT, elicited Cl- currents through activation of the phosphatidylinositol/Ca2+ messenger pathway. The two types of 5-HT receptors showed similar sensitivity to dopamine; threshold responses were activated at concentrations as low as 1 microM. However, maximum dopamine responses were only 5-20% of maximum responses activated by 5-HT. The dopamine D1 receptor antagonist SCH 23390 was a potent agonist on 5-HT1c and 5-HT2 receptors. SCH 23390 elicited currents at concentrations as low as 1 nM, but maximum responses were again only 5-20% of those activated by 5-HT. Fenoldopam, a dopamine D1 receptor agonist, also interacted with 5-HT1c and 5-HT2 receptors, eliciting threshold responses between 10 and 20 nM. Our experiments raise the possibility that low micromolar concentrations of dopamine can cause weak activation and concomitant desensitization of serotoninergic systems in vivo and demonstrate that benzazepines can interact with 5-HT receptors at nanomolar concentrations.