Tseng L F
J Pharmacol Exp Ther. 1986 Oct;239(1):160-5.
The author has previously reported that i.c.v. beta-endorphin increases the release of immunoreactive Met-enkephalin from the spinal cord. The present studies were conducted to study the effects of beta-endorphin and its position 5 amino acid-substituted analogs on the production of analgesia and the spinal release of Met-enkephalin in rats. Analgesia was measured by tail-flick test in conscious rats, and the release of Met-enkephalin from the spinal cord was studied in urethane-anesthetized rats using a technique of spinal superfusion. beta-Endorphin (0.8-40 micrograms i.c.v.) inhibited the tail-flick response in a dose-related manner, whereas D-Met5-beta-endorphin, even at the highest dose, 40 micrograms, was unable to inhibit the tail-flick response. L- and D-Leu5-beta-endorphin inhibited the tail-flick response only at high doses, with the D-isomer being slightly more potent than the L-isomer. Human beta-endorphin (0.8-16 micrograms i.c.v.) caused a dose-dependent increase of Met-enkephalin release from the spinal cord, whereas D-Met5-beta-endorphin, even at a high dose (16 micrograms), showed no release of Met-enkephalin. Leu5-beta-endorphin and D-Leu5-beta-endorphin showed little or no release of Met-enkephalin. The results indicate that beta-endorphin shows stereoselectivity on the production of analgesia and the release of Met-enkephalin.
作者之前曾报道，脑室内注射β-内啡肽可增加脊髓中免疫反应性甲硫氨酸脑啡肽的释放。本研究旨在探讨β-内啡肽及其5位氨基酸取代类似物对大鼠镇痛作用及脊髓中甲硫氨酸脑啡肽释放的影响。通过对清醒大鼠进行甩尾试验来测定镇痛效果，并采用脊髓灌流技术研究了在乌拉坦麻醉大鼠中脊髓中甲硫氨酸脑啡肽的释放情况。β-内啡肽（脑室内注射0.8 - 40微克）以剂量相关的方式抑制甩尾反应，而D-蛋氨酸5-β-内啡肽即使在最高剂量40微克时也无法抑制甩尾反应。L-和D-亮氨酸5-β-内啡肽仅在高剂量时抑制甩尾反应，其中D-异构体的效力略强于L-异构体。人β-内啡肽（脑室内注射0.8 - 16微克）导致脊髓中甲硫氨酸脑啡肽释放呈剂量依赖性增加，而D-蛋氨酸5-β-内啡肽即使在高剂量（16微克）时也未显示甲硫氨酸脑啡肽的释放。亮氨酸5-β-内啡肽和D-亮氨酸5-β-内啡肽显示甲硫氨酸脑啡肽释放很少或没有释放。结果表明，β-内啡肽在镇痛作用及甲硫氨酸脑啡肽释放方面表现出立体选择性。
