Rezvani A, Way E L
Eur J Pharmacol. 1984 Jul 20;102(3-4):475-9. doi: 10.1016/0014-2999(84)90568-5.
Since it has been reported that dynorphin (1-13) enhances the analgetic effects of morphine in mice tolerant either to morphine or beta-endorphin and modulates opioid agonist binding in the tolerant state, experiments were initiated to determine whether comparable phenomenon could be obtained in vitro with dynorphin-(1-13) on the isolated longitudinal muscle of the guinea pig ileum. In the guinea pig ileum rendered tolerant to morphine dynorphin-(1-13) was found to cause a dose-dependent restoration in sensitivity to the inhibitory action of morphine. This phenomenon appeared specific for dynorphin-(1-13) since [Leu5]enkephalin, beta-endorphin, and ethylketocyclazocine did not change significantly the IC50 of morphine in the tolerant preparation. Furthermore, dynorphin-(1-13) attenuated the contraction elicited by naloxone in the morphine tolerant-dependent tissue. It is concluded, that dynorphin-(1-13) restores sensitivity to morphine in the tolerant-dependent state by a modulatory effect probably on the mu receptor that is distinct from its kappa action.
由于有报道称强啡肽（1-13）可增强对吗啡或β-内啡肽耐受的小鼠体内吗啡的镇痛作用，并在耐受状态下调节阿片类激动剂的结合，因此开展了实验以确定在体外，强啡肽（1-13）对豚鼠回肠的离体纵行肌是否能产生类似现象。在对吗啡产生耐受的豚鼠回肠中，发现强啡肽（1-13）可使对吗啡抑制作用的敏感性呈剂量依赖性恢复。这一现象似乎对强啡肽（1-13）具有特异性，因为亮氨酸脑啡肽[Leu5]、β-内啡肽和乙基酮环唑辛在耐受制剂中并未显著改变吗啡的半数抑制浓度（IC50）。此外，强啡肽（1-13）减弱了纳洛酮在吗啡耐受依赖性组织中引起的收缩。得出的结论是，强啡肽（1-13）可能通过对μ受体的调节作用，在耐受依赖性状态下恢复对吗啡的敏感性，这种调节作用与其κ作用不同。
