The "selective" dopamine D1 receptor antagonist, SCH23390, is a potent and high efficacy agonist at cloned human serotonin2C receptors
The "selective" dopamine D1 receptor antagonist, SCH23390, is a potent and high efficacy agonist at cloned human serotonin2C receptors
复制标题
DOI：
10.1007/s002130100742
复制
发表时间：
2001-06-01
影响因子：
3.4
通讯作者：
Cussac, D
中科院分区：
文献类型：
--
作者：
Millan, MJ;Newman-Tancredi, A;Cussac, D
理由：苯氮平和“选择性”多巴胺DI受体拮抗剂SCH23390 [(R)-(+)8-氯-2,3,4,5-四氢-3-甲基-5-苯基- 1h -苯氮平-7-醇]对天然5-羟色胺（5-HT）（2C）受体具有显著的亲和力。目的：研究其对CHO细胞中稳定表达的克隆人(h)5-HT2C受体（VSV亚型）的功能作用。方法：由于5-HT2C受体与磷脂酶C （PLC）正偶联，因此通过耗尽预标记的[H-3]磷脂酰肌醇（[H-3]PI）的膜结合池来确定其激活。结果：SCH23390对h5-HT2C位点具有较高的亲和力（K-i, 9.3 nM），并能降解[H-3]PI， EC50为2.6 nM。其疗效与5-HT相当。SCH23390引起的[H-3]PI耗竭被选择性5-HT2C拮抗剂sb242084以浓度依赖性消除，K-B值为0.55 nM。此外，在固定浓度的sb242084 （10 nM）存在下，SCH23390的浓度-响应曲线向右移动而没有失去最大效果，K-B为0.57 nM。结论：SCH23390是一种有效的h5-HT2C受体激动剂。SCH23390激活5-HT2C受体可能有助于其在动物和人类中的功能特性。
Rationale: The benzazepine and "selective" dopamine DI receptor antagonist, SCH23390 [(R)-(+)8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7-ol], shows significant affinity at native serotonin (5-HT)(2C) receptors. Objectives: We examined its functional actions at cloned human (h)5-HT2C receptors (VSV isoform) stably expressed in CHO cells. Methods: Since 5-HT2C receptors are positively coupled to phospholipase C (PLC), their activation was determined by depletion of membrane-bound pools of pre-labelled [H-3]phosphotidylinositol ([H-3]PI). Results: SCH23390 showed high affinity (K-i, 9.3 nM) at h5-HT2C sites and depleted [H-3]PI with an EC50 of 2.6 nM. Its efficacy was equivalent to that of 5-HT. [H-3]PI depletion elicited by SCH23390 was concentration-dependently abolished by the selective 5-HT2C antagonist, SB242,084, with a K-B Of 0.55 nM. Further, in the presence of a fixed concentration of SB242,084 (10 nM), the concentration-response curve for SCH23390 was shifted to the right without loss of maximal effect, yielding a K-B of 0.57 nM. Conclusions: SCH23390 is a potent and high efficacy agonist at h5-HT2C receptors. Activation of 5-HT2C receptors by SCH23390 may contribute to its functional properties both in animals and in humans.