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）在人血小板上存在5HT-2受体作为血清素能神经元某些功能的易于访问的外围模型，可以直接研究活人中5HT-2受体的功能。在本研究中，我们已经评估了正常对照组的血小板中5HT刺激的磷酸肌醇水解和治疗前抑郁症。在一组与正常对照组相匹配的重度抑郁症患者的一组未药物的患者中，我们发现5HT（100UM）诱导的肌醇1-磷酸盐（IP-1）的积累显着增加，这是Phoshpoinsitide水解的一种代谢产物（抑郁症患者的基础150 7％，对照组为150 7％，对照组13％）。该结果表明，5HT刺激的磷酸肌醇代谢，由5HT-2受体在血小板中介导它们对河马片中的这种5HT响应有任何影响。利坦氏素抑制5HT刺激的IP-1积累，Ki值为20nm。 Mianserin（1UM），Ketanserin（1UM）和MCPP（100UM）部分减少了5HT刺激的IP-1积累；螺旋酮（1UM）和普萘洛尔（1UM）无法阻止5HT响应。这些结果表明，5HT通过Hippocampla切片中的5HT-2和5HT-1C PI反应受体介导其5HT受体在磷酸肌醇水解上介导。对抑郁型PCPA的10天治疗导致IP-1的响应显着增加。