Kusumi I, Mikuni M, Kuroda Y, Takahashi K
Division of Mental Disorder Research, National Institute of Neuroscience, Tokyo, Japan.
J Neural Transm Gen Sect. 1990;80(3):181-8. doi: 10.1007/BF01245119.
Serotonin (5-HT) caused a dose-dependent accumulation of inositol monophosphate (IP-1) in rat hippocampal slices (maximal effect + 172%, EC50 = 630 nM) in the presence of LiCl. The 5-HT response was blocked potently by a non-selective 5-HT receptor antagonist metergoline and a 5-HT1C/5-HT2 receptor antagonist ritanserin. The 5-HT2 receptor antagonist ketanserin and spiperone were, however, less potent at inhibiting the 5-HT response. m-Chlorophenylpiperazine (mCPP), a 5-HT1C receptor agonist but a 5-HT2 antagonist stimulated directly PI turnover, yet mCPP inhibited 5-HT-stimulated PI response. These findings indicate that both 5-HT1C and 5-HT2 receptors are involved with a complicated interaction of each receptor in 5-HT-stimulated PI hydrolysis in rat hippocampus. 10-Day treatment with para-chlorophenyl-alanine (PCPA), a 5-HT synthesis inhibitor, resulted in a significant increase (maximal effect + 225%, EC50 = 580 nM) in 5-HT-stimulated IP-1 accumulation with no substantial change in EC50 value, which suggest that subchronic treatment with PCPA enhances the 5-HT-mediated PI hydrolysis in rat hippocampus.
在存在氯化锂的情况下，血清素（5-羟色胺，5-HT）使大鼠海马切片中的肌醇单磷酸（IP-1）呈剂量依赖性积累（最大效应为 +172%，半数有效浓度EC50 = 630 nM）。5-HT反应被非选择性5-HT受体拮抗剂美替拉酮和5-HT1C/5-HT2受体拮抗剂利坦色林有效阻断。然而，5-HT2受体拮抗剂酮色林和螺哌隆在抑制5-HT反应方面的效力较低。间氯苯哌嗪（mCPP）是一种5-HT1C受体激动剂但为5-HT2拮抗剂，它直接刺激磷脂酰肌醇（PI）周转，然而mCPP抑制5-HT刺激的PI反应。这些发现表明，在大鼠海马中5-HT刺激的PI水解过程中，5-HT1C和5-HT2受体均参与其中，且各受体之间存在复杂的相互作用。用5-HT合成抑制剂对氯苯丙氨酸（PCPA）进行为期10天的处理，导致5-HT刺激的IP-1积累显著增加（最大效应为 +225%，EC50 = 580 nM），而EC50值无实质性变化，这表明用PCPA进行亚慢性处理可增强大鼠海马中5-HT介导的PI水解。
