Nemeroff C B, Osbahr A J, Manberg P J, Ervin G N, Prange A J
Proc Natl Acad Sci U S A. 1979 Oct;76(10):5368-71. doi: 10.1073/pnas.76.10.5368.
The antinociceptive and hypothermic effects of intracisternal administration of 11 endogenous neuropeptides and morphine were evaluated in mice. Of the substances tested, only neurotensin (NT) and beta-endorphin exerted significant antinociceptive and hypothermic effects; NT was the most potent in inducing hypothermia whereas beta-endorphin was the most potent antinociceptive agent via this route of administration. Both NT, and beta-endorphin were, on a molar basis, considerably more potent antinociceptive agents than morphine, [Met]enkephalin, or [Leu]enkephalin. NT-induced analgesia and hypothermia both were significantly dose-dependent. Substance P was found to produce significant hyperalgesia and hyperthermia. Bombesin produced a significant hypothermic effect, whereas somatostatin and luteinizing hormone-releasing hormone (luliberin) produced hyperthermia. None of the other peptides studies [bradykinin, thyrotropin-releasing factor (thyroliberin), melanocyte-stimulating hormone release-inhibiting factor (melanostatin), somatostatin, [Met]enkephalin, and [Leu]enkephalin] produced any significant alterations in colonic temperature or response to a noxious stimulus with the doses tested. These data demonstrate that NT and beta-endorphin, two endogenous brain peptides, are potent in inducing hypothermia and in producing an antinociceptive state.
通过向小鼠脑池内注射11种内源性神经肽和吗啡,评估了它们的镇痛和降温作用。在所测试的物质中,只有神经降压素(NT)和β-内啡肽具有显著的镇痛和降温作用;NT诱导降温的作用最强,而β-内啡肽通过这种给药途径是最有效的镇痛剂。按摩尔计算,NT和β-内啡肽作为镇痛剂都比吗啡、[甲硫氨酸]脑啡肽或[亮氨酸]脑啡肽有效得多。NT诱导的镇痛和降温作用均呈显著的剂量依赖性。发现P物质可产生显著的痛觉过敏和体温升高。蛙皮素可产生显著的降温作用,而生长抑素和促黄体生成素释放激素(促性腺激素释放激素)可使体温升高。其他研究的肽类[缓激肽、促甲状腺激素释放因子(促甲状腺素释放激素)、促黑素释放抑制因子(黑素抑制素)、生长抑素、[甲硫氨酸]脑啡肽和[亮氨酸]脑啡肽]在所测试的剂量下均未引起结肠温度或对有害刺激的反应有任何显著改变。这些数据表明,NT和β-内啡肽这两种内源性脑肽在诱导降温和产生镇痛状态方面很有效。