Intrathecal cholecystokinin octapeptide attenuates the antinociception and release of immunoreactive Met-enkephalin induced by intraventricular beta-endorphin in the rat.
The effects of cholecystokinin octapeptide (CCK8s) given intrathecally (i.t.) on antinociception and the release of immunoreactive Met-enkephalin in the spinal perfusate induced by intraventricular (i.vt.) injection of beta-endorphin were studied in anesthetized rats. beta-Endorphin (5 micrograms) given i.vt. inhibited the tail-flick response. The inhibition of the tail-flick response induced by beta-endorphin was blocked dose-dependently by CCK8s (0.1-7 micrograms) given i.t. The antagonistic effect of CCK8s on beta-endorphin-induced inhibition was blocked dose dependently by co-intrathecal injection of proglumide (3 and 10 micrograms), a CCK8s receptor antagonist. beta-Endorphin (5 micrograms) given i.vt. elicited a release of immunoreactive Met-enkephalin in the spinal perfusate. Repeated injections of the same dose of beta-endorphin released about the same amount of the immunoreactive Met-enkephalin in the spinal perfusate. CCK8s at concentrations from 1 x 10(-9) to 1 x 10(-6) M added into the spinal perfusate decreased the release of Met-enkephalin induced by beta-endorphin given i.vt. in a dose-dependent manner. The results suggest that CCK8s may attenuate beta-endorphin-induced inhibition of the tail-flick response by inhibiting the release of Met-enkephalin from the spinal cord.
Suh
H H
HH
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Collins
K A
KA
Tseng
L F
LF
D000818:Animals; D003864:Depression, Chemical; D004744:Enkephalin, Methionine / Q000378:metabolism*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D009292:Narcotic Antagonists; D010146:Pain / Q000503:physiopathology*; D011377:Proglumide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017465:Receptors, Opioid, delta; D012018:Reflex / Q000187:drug effects; D012636:Secretory Rate / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology*; D013116:Spinal Cord / Q000503:physiopathology; D013623:Tail; D001615:beta-Endorphin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D011377:Proglumide; D012844:Sincalide