Increased release of immunoreactive cholecystokinin octapeptide by morphine and potentiation of mu-opioid analgesia by CCKB receptor antagonist L-365,260 in rat spinal cord.
Increased release of immunoreactive cholecystokinin octapeptide by morphine and potentiation of mu-opioid analgesia by CCKB receptor antagonist L-365,260 in rat spinal cord.
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在大鼠脊髓中吗啡增加了免疫反应性胆囊收缩素八肽的释放，CCKB 受体拮抗剂 L-365,260 增强了 mu-阿片类镇痛作用。
DOI：
10.1016/0014-2999(93)90948-h
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发表时间：
1993
影响因子：
5
通讯作者：
Han,JS
中科院分区：
文献类型：
--
作者：
Zhou,Y;Sun,YH;Zhang,ZW;Han,JS
本文首次报道了在体研究中，全身注射吗啡可使大鼠脊髓灌流液中八肽胆囊收缩素（CCK-8）的免疫反应性显著增加（89%，P < 0.01），而纳洛酮可完全逆转这种作用。由于CCK-8已被证明在脊髓水平具有有效的抗阿片活性，因此预期脊髓胆囊收缩素效应的阻断将增强阿片镇痛。以甩尾潜伏期为伤害性指标，发现鞘内（i.t.）腹腔注射新型CCK-8拮抗剂L-365，260可明显增强μ阿片受体激动剂吗啡（4 mg/kg s.c.）或羟甲芬太尼（32 ng i.t.）。CCKA拮抗剂devazepide在剂量比L-365，260高40-50倍时也获得了类似的效果。地伐卓和L-365，260均显示钟形剂量-反应曲线。结果证实了CCK-8释放增加可能构成脊髓水平阿片效应的自限性过程，CCK-8受体介导了CCK-8在脊髓的抗阿片效应。
This is the first report showing, in an in vivo study, that systematic morphine produced a marked (89%, P < 0.01) increase of the cholecystokinin octapeptide (CCK-8) immunoreactivity in the perfusate of the rat spinal cord, an effect completely reversed by naloxone. Since CCK-8 has been shown to possess potent anti-opioid activitit at a spinal level, a blockade of the spinal cholecystokinin effect would be expected to potentiate opiate analgesia. With tail flick latency as a nociceptive index, it was found that intrathecal (i.t.) injection of a novel CCKBantagonist L-365,260 produced a marked potentiation of the analgesic effect induced by the μ-opioid agonists morphine (4 mg/kg s.c.) or ohmefentanyl (32 ng i.t.). Similar effects were obtained with the CCKAantagonist devazepide at a dose 40–50 times higher than that of L-365,260. Both devazepide and L-365,260 showed a bell-shaped dose-response curve. The results confirm the notion that an increased release of CCK-8 may constitute a self-limiting process for opioid effects at the spinal level, and that it is the CCKBreceptor which mediates the anti-opioid effect of CCK-8 in the rat spinal cord.