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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) 5HT-2受体在人血小板上的存在，作为血清素能神经元某些功能的容易接近的外周模型，可能允许直接研究5HT-2受体在活人中的功能。在本研究中，我们评估了治疗前正常对照组和抑郁症患者的血小板中5ht刺激的磷酸肌肽水解。在一组与正常对照组年龄相匹配的未服药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）的积累显著增加，肌醇-1-磷酸是磷苷水解的一种代谢产物（抑郁症患者为基础患者的157%，对照组为133%）。提示5HT-2受体介导的5ht刺激的磷酸肌肽代谢可能是研究抑郁症患者血清素能受体功能的有效手段。2)我们研究了5HT刺激的大鼠海马切片中IP-1的积累是否由5HT-2受体介导，以及亚慢性给药PCPA、丙嗪及其联合用药对海马切片中这种5HT反应的影响。利坦色林抑制5ht刺激的IP-1积累，Ki值为20nM。眠色林（1uM）、酮色林（1uM）和mCPP（100uM）部分减少5ht刺激的IP-1积累；spiperone（1uM）和心得安（1uM）未能阻断5HT反应。这些结果表明5HT通过5HT-2和5HT-1c PI反应受体在海马切片中介导其5HT受体磷酸化肌肽水解。经PCPA治疗10天后，患者的IP-1反应明显升高。