八肽胆囊收缩素对抗mu和Kappa型受体介导的镇痛作用

以往的资料表明,八肽胆襄收缩素(CCK-8)能对抗阿片镇痛,本实验进一步分析 CCK-8对抗哪一类型阿片受体激动剂的镇痛作用。给大鼠脊髓蛛网膜下腔(I.T.)注射 CCK-8(剂量4ng到1.0μg)既不产生痛敏也不产生镇痛。I.T.注射特异性的μ受体激动剂 PL01710 ng 或 k 受体激动剂 NDA P500 ng 引起的镇痛作用可被注射 CCK-8 4ng 所对抗。而L.T.注射δ受体激动剂 DPDPE(6.5,13.0和26.Oμg)引起的镇痛作用不能被 CCK-8(4ng,40ng I.T.)所对抗。但 CCK-8对抗 PL017和 NDAP 镇痛的作用可被 I.T.CCK 受体拮抗剂 proglumide(3μg)所翻转。以上结果表明,I.T.注射 CCK-8可有效地对抗μ和 k 受体介导的镇痛,并且这种对抗作用是经 CCK 受体介导而实现的。

CHOLECYSTOKININ OCTAPEPTIDE(CCK-8)ANTAGONIZED NALGESIA MEDIATED BY MU AND KAPPA OPIOID RECEPTORS

CCK-8 has been shown to antagonize the analgesia produced by morphine or endogenous opioid peptides. The present study was performed to clarify the interaction between CCK-8 and different opioid ligands. Analgesia produced by intrathecal (I.T.) injection of the specific mu receptor agonist PL017 10 ng or kappa receptor agonist NDAP 500 ng can be antagonized by I.T. injection CCK-8 at a dose as small as 4 ng. In contrast, analgesia produced by I.T. injection of the delta receptor agonist DPDPE (6.5, 13 and 26 micrograms) was not blocked by CCK-8 (4 ng or 40 ng, I.T.). The antagonistic effect of CCK-8 on PL017 and NDAP could be completely reversed by proglumide (3 micrograms, I.T.). I.T. injection of CCK-8 (4 or 40 ng single dose or cumulative dose of 0.1, 0.2, 0.5 and 1.0 microgram at 10 min intervals) produced neither analgesia nor hyperalgesia. In conclusion, CCK-8 preferentially antagonizes opioid analgesia mediated by mu and kappa receptors, and this antagonistic effect is mediated by CCK receptors.