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Study on the function of monoamine receptors and transmembrane signal control in the affective disorders.

情感障碍中单胺受体功能和跨膜信号控制的研究。

基本信息

批准号：
62570482
负责人：
MIKUNI Masahiko
金额：
$ 1.22万
依托单位：
Div. of Mental Disorder Res., Natl. Institute of Neuroscience, NCNP
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

1) The presence of 5HT-2 receptors on the human platelets as a readily accessable peripheral model for certain functions of the serotonergic neuron, may permit direct study of the function of 5HT-2 receptors in living persons. In the present study, we have assessed 5HT-stimulated phosphoinositide hydrolysis in platelets from a normal control group and depressed subjects before treatment. In a group of unmedicated patients with major depressive disorder matched for age with normal control group, we found a significant increase in 5HT(100uM)-induced accumulation of inositol-1-phosphate(IP-1), one metabolic product of phoshpoinositide hydrolysis(150 7% of basal for depressed patients, 132 3% for controls). This result suggested that 5HT-stimulated phosphoinositide metabolism, mediated by 5HT-2 receptors in platelets might be provide a useful mean of investigating serotonergic receptor function in depressed patients.2) We investigated whether 5HT-stimulated IP-1 accumulation in rat hippocampla slices is mediated by the 5HT-2 receptors, and a subchronic administration of PCPA, imipramine and in combination thereof has any effect on this 5HT response in the hippocampla slices. Ritanserin inhibit 5HT-stimulated IP-1 accumulation with a Ki value of 20nM. Mianserin(1uM), ketanserin(1uM) and mCPP(100uM) reduced partially 5HT-stimulated IP-1 accumulation; spiperone(1uM) and propranolol(1uM) failed to block the 5HT response. These results indicated that 5HT mediates its 5HT receptor on phosphoinositide hydrolysis through the 5HT-2 and 5HT-1c PI response receptors in the hippocampla slices. The 10-day treatment with Depression PCPA resulted in a significant increase in response of IP-1.

1) 人类血小板上存在 5HT-2 受体，作为血清素能神经元某些功能的易于获得的外周模型，可能允许直接研究活人中 5HT-2 受体的功能。在本研究中，我们在治疗前评估了正常对照组和抑郁受试者血小板中 5HT 刺激的磷酸肌醇水解情况。在一组与正常对照组年龄相匹配的未接受药物治疗的重度抑郁症患者中，我们发现5HT（100uM）诱导的肌醇-1-磷酸（IP-1）（磷酸肌醇水解的一种代谢产物）的积累显着增加（抑郁症患者为基础值的150±7％，对照组为132±3％）。这一结果表明，由血小板中的 5HT-2 受体介导的 5HT 刺激的磷酸肌醇代谢可能为研究抑郁症患者的血清素受体功能提供有用的方法。2) 我们研究了大鼠海马切片中 5HT 刺激的 IP-1 积累是否由 5HT-2 受体介导，以及 PCPA、丙咪嗪和组合的亚慢性给药它对海马切片中的 5HT 反应有任何影响。 Ritanserin 抑制 5HT 刺激的 IP-1 积累，Ki 值为 20nM。 Mianserin(1uM)、ketanserin(1uM) 和 mCPP(100uM) 部分减少 5HT 刺激的 IP-1 积累；螺哌隆(1uM)和普萘洛尔(1uM)未能阻断5HT反应。这些结果表明5HT通过海马切片中的5HT-2和5HT-1c PI反应受体介导其5HT受体对磷酸肌醇的水解。为期 10 天的抑郁 PCPA 治疗导致 IP-1 反应显着增加。