Inhibition of tolerance to the pharmacological effects of human beta-endorphin by prolyl-leucyl-glycinamide and cyclo(leucylglycine) in the rat.
Inhibition of tolerance to the pharmacological effects of human beta-endorphin by prolyl-leucyl-glycinamide and cyclo(leucylglycine) in the rat.
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发表时间：
1981-08
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通讯作者：
H. Bhargava
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作者：
H. Bhargava
急性脑室内注射人β-内啡肽（15微克）在雄性Sprague-Dawley大鼠中产生镇痛、体温过低和僵硬。每8小时注射β-内啡肽，持续3天，导致对所有上述药理作用的耐受性的发展。耐受性迅速发展的低温效应和不太迅速的镇痛和僵硬的影响。在第三次或第四次注射β-内啡肽后，观察到明显的体温过高，而不是体温过低。在注射了7或8次β-内啡肽后，对镇痛作用的耐受性完全恢复，僵硬作用减少到原来的50%。每日皮下注射给予Pro-Leu-Gly-NH 2（MIF）或cyclo（Leu-Gly）（各2 mg/kg）阻断了对β-内啡肽的镇痛和僵硬作用的耐受性的发展。在β-内啡肽耐受大鼠中，β-内啡肽的过热效应可被MIF和环（Leu-Gly）部分阻断。多次注射MIF或cyclo（Leu-Gly）并没有改变β-内啡肽诱导的镇痛，僵硬症和体温过低的大鼠，反复脑室内注射生理盐水。由于MIF是一种天然存在的肽的下丘脑起源，这些研究表明，下丘脑可能是一个重要的网站，在调节长期管理的内源性阿片类药物的药理作用。
Acute intraventricular administration of human beta-endorphin (15 microgram) produced analgesia, hypothermia and catalepsy in male Sprague-Dawley rats. Injections of beta-endorphin given every 8 hr for 3 days resulted in the development of tolerance to all of the above mentioned pharmacological effects. Tolerance developed rapidly to the hypothermic effect and less rapidly to the analgesic and cataleptic effects. After the third or the fourth injection of beta-endorphin, pronounced hyperthermia, rather than hypothermia, was observed. After seven or eight injections of beta-endorphin, tolerance to the analgesic effect was complete and the cataleptic effect was reduced to 50% of the original. Daily s.c. administration of Pro-Leu-Gly-NH2 (MIF) or cyclo(Leu-Gly) (2 mg/kg each) blocked the development of tolerance to the analgesic and cataleptic effects of beta-endorphin. The hyperthermic effect of beta-endorphin in beta-endorphin-tolerant rats was partially blocked by both MIF and cyclo(Leu-Gly). Multiple injections of MIF or cyclo(Leu-Gly) did not alter beta-endorphin-induced analgesia, catalepsy and hypothermia in rats which were given repeated intraventricular injections of saline. Since MIF is a naturally occurring peptide of hypothalamic origin, these studies suggest that the hypothalamus may be an important site in regulating the pharmacological effects of chronically administered endogenous opiates.