Clarification Of Physiological Significance of endogenous antiopiates and their application for the drug development.

阐明内源性安替阿片的生理意义及其在药物开发中的应用。

基本信息

批准号：
08672514
负责人：
TAKAHASHI Masakatsu
金额：
$ 1.47万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

The anaticipated role of "antiopiates", which believe to modulate endogenous pain inhibitory system, is still unclear ; both the anti-analgesic effect of Tyr-MIF-1 (Tyr-Pro-Leu-Gly amide), one of the antiopiate candidate, and its derivativ, YPIG (Tyr-Pro-Ile-Gly amide), and the effect of these peptides on emotionallity and leaning/memory processes, were investigated in mice.Tyr-MIF-1, when administered intraperetoneally (i.p.) or intrathecally, significantly attenuated the antinociceptive effect of both morphine and U-50488, mu and kappa opioid receptor agonist, respectively, but the peptide given intracerebroventricularly (i.c.v.) had no effect on these antinociceptive effects. Tyr-MIF-1 given i.p. but not i.c.v.also inhibited antinociception induced by DPDPE,a delta receptor agonist. I.c.v.YPIG potetiated morphine analgesia while leaving antinociception by U-50,488H unaffected.Tyr-MIF-1 suppressed not only footshock (FS) - and socio-psychological (PSY)- stress-induced analgesia (SLA) … More , both are naloxone reversible, but also naloxone insensitive forced swim (SW) -SIA.YPIG given i.p.blocked FS- and PSY-SLA ; however, i.c.v.YPIG augmented antinociception induced by FS-, PSY- and SW-stress.The suppressive effect of FS- and PSY-stress on the development of morphine tolerance was extinguished by Tyr-MIF-1 and YPIG given i.p.Tyr-MLF-1 increased time spent open arm in the elevated plus maze test, suggesting anxiolytic properties of the peptide.Tyr-MIF-1 had no effect on the learning/memory precesses in one trial passive avoidance test.In experiment of mu opioid receptor binding assay, the affinity of Tyr-MIF-1 was about five times lower than that of YPIG.Taken together, these results imply the inclusive involvement of Tyr-MIF-1 in the modulation of the adaptive mechanisms, including pain-inhibitory systems and emotionality. The stereospecific structure seems required for the production of anitopiate effect of Tyr-MIF-1, from the distinct effects induced by Tyr-MIF-1 and YPIG.In addition, the physiological and pharmacological role of another candidate of antlopiates, complement C3a, is now undertaken to clarify. Less

“反pite”的Anaticated作用仍然不清楚，后者认为调节内源性疼痛抑制系统。 Tyr-Mif-1（Tyr-Pro-Leu-Gly amide）的抗抗痛性作用，抗opite候选者之一及其衍生物Ypig（Tyr-Pro-ile-Gly-Gly amide），以及这些肽对小时或内加性（Inciply）incect.tyr-mif-1的影响，这些肽对情感联盟和倾斜/记忆过程的影响（I.分别减弱了吗啡和U-50488，MU和Kappa Ooid受体激动剂的抗毒素作用，但是对脑外进行了肽（i.c.v.）的肽对这些抗心敏感效应没有影响。 Tyr-Mif-1给了i.p.但不是I.C.V.也抑制了由三角洲受体激动剂DPDPE诱导的抗伤害感受。 I.C.V.型肥大的吗啡镇痛作用，同时不受U-50,488H不受影响。Tyr-Mif-1不仅抑制了脚垫（FS）和社会心理学（PSY） - 压力诱导的镇痛（SLA）……更多，而且都可以逆转，而且都可以逆转，而且是naloxone s的nalox nemige semip。 FS和PSY-SLA; however, i.c.v.YPIG augmented antinociception induced by FS-, PSY- and SW-stress.The suppressive effect of FS- and PSY-stress on the development of morphine tolerance was extended by Tyr-MIF-1 and YPIG given i.p.Tyr-MLF-1 increased time spent open arm in the elevated plus maze test, suggesting anxiolytic properties of the pepper.Tyr-MIF-1 had no effect on the learning/memory在一次试验的被动回避测试中，进攻性。在MU阿片受体结合测定的实验中，Tyr-Mif-1的亲和力比Ypig的亲和力低约五倍，这些结果是Tyr-Mif-1的包含在适应性机制的调节中，包括抑制疼痛抑制性系统和情感性。从Tyr-Mif-1和Ypig引起的明显效应的产生的抗氧化作用似乎是立体特异性结构，此外，另一种候选Antlopiates的物理和药物作用，即“完成C3A”，现在是为了澄清的。较少的