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.
This is the first report showing, in an in vivo study, that systemic 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 activity 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 CCKB antagonist L-365,260 produced a marked potentiation of the analgesic effect induced by the mu-opioid agonists morphine (4 mg/kg s.c.) or ohmefentanyl (32 ng i.t.). Similar effects were obtained with the CCKA antagonist 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 CCKB receptor which mediates the anti-opioid effect of CCK-8 in the rat spinal cord.
Neuroscience Research Center, Beijing Medical University, People's Republic of China.
Y
Y
Zhou
Y H
YH
Sun
Z W
ZW
Zhang
J S
JS
Han
D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000031:analogs & derivatives / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010671:Phenylurea Compounds; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D012844:Sincalide / Q000276:immunology / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013346:Subarachnoid Space / Q000502:physiology
D000700:Analgesics; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D017450:Receptors, Opioid, mu; D009270:Naloxone; C058121:L 365260; D009020:Morphine; C037016:F 7302; D020109:Devazepide; D012844:Sincalide; D005283:Fentanyl