胆囊收缩素受体拮抗剂加强大鼠的吗啡镇痛和羟甲芬太尼镇痛

POTENTIATION OF MORPHINE-AND OHMEFENTANYL-INDUCED ANALGESIA BY CHOLECYSTOKININ RECEPTOR ANTAGONISTS IN RAT

已知大鼠脊髓蛛网膜下腔(i.t.)注射CCK-8能拮抗阿片μ受体介导的镇痛作用。本文给大鼠i.t.注射高选择性CCK-A受体拮抗剂devazepide和CCK-B受体拮抗剂L-365260阻断内源性释放的CCK-8,观察对阿片镇痛的影响。i.t.注射100ng devazepide或2.5ng L-365260可显著地增强吗啡镇痛(4mg/kg,sc),两者的剂量效应曲线均为钟形曲线;i.t.注射66ng devazepide或1.25ng L-365260也能显著地增强羟甲芬太尼(专一的阿片μ受体激动剂,OMF)的镇痛作用(32ng,i.t.),剂量效应曲线亦为钟形曲线。这两种CCK受体拮抗剂本身对病阈无影响。 以上结果表明,脊髓内有内源性CCK-8发挥对抗阿片镇痛作用;鉴于devazepide剂量大于L-365260剂量40-50倍,提示CCK-8在脊髓的抗阿片镇痛功能是通过CCK-B受体实现的。

It has been reported that intrathecal (i.t.) injection of CCK-8 showed a markedantugonism to analgesic effects mediated by μ-opioid receptors in rat. The present studywas performed to ascertain whether the blockade of endogenously released CCK--8 by po-tent and selective CCK--A antagonist devazepide and CCK--B antagonist L-365260 wouldaffect opioid analgesia at the spinal cord level. A marked poentiation of the analgesic effect induced by morphine (4 mg/kg,sc) was produced by i. t. injection of 100 ng devazepide or 2. 5 ng L--365260. Dose-resthese curves for the enhancement of the two drugs on morphine analgesia were bell-shaped. Intrathecal injection of 66 ng devazepide or 1.25 ng L- 365260 was alsoshown to potentiate the analgesic effect induced by the selective μ--opioid agonist ohme-fentanyl (OMF) (32 ng, i. t. ). The dose--response curves were also bell--shaped. De-vazepide or L-365260 per se produced no significant changes in rat tail flick latency(TFL). The above results are interpreted to mean that endogenously released CCK--8 in thespinal cotd plays an antagonistic role to opioid analgesia, and it is the CCK-B receptorsthat mediate the anti--opioid effect since the dose of devazepide is 40--50 times higherthan that of L-365260.