Cholecystokinin administered intrathecally selectively antagonizes intracerebroventricular beta-endorphin-induced tail-flick inhibition in the mouse.
The effects of sulfated cholecystokinin octapeptide (CCK8s) given intrathecally (i.t.) or intracerebroventricularly (i.c.v.) on inhibition of the tail-flick and paw-licking hot-plate responses induced by beta-endorphin, morphine, D-Ala2-N-Me-Phe4-Gly-ol-Enkephalin (DAMGO) and D-Pen2-D-Pen5-Enkephalin (DPDPE), given i.t. or i.c.v., were studied in male ICR mice. CCK8s (1 ng) given i.t. effectively antagonized inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin (2 micrograms) and DPDPE (10 micrograms) but not morphine (4 micrograms) or DAMGO (0.02 microgram). However, CCK8s given i.t. did not affect inhibition of the hot-plate response induced by any of the opioid agonists. CCK8s (0.2-40 ng) in combination with beta-endorphin (2 micrograms) or morphine (4 micrograms) given i.c.v. did not affect beta-endorphin- or morphine-induced inhibition of the tail-flick and hot-plate responses. CCK8s and its fragments given i.t. attenuated i.c.v. beta-endorphin-induced tail-flick inhibition with different potencies and efficacies. CCK8s was the most potent compound in antagonizing i.c.v. beta-endorphin-induced tail-flick inhibition. The rank order of potencies was CCK8s greater than CCK(27-33) much greater than caerulein. All three compounds were efficacious, whereas CCK(30-33) was not, in antagonizing beta-endorphin-induced tail-flick inhibition. Intrathecal administration of CCK8s (1 ng) significantly attenuated the tail-flick inhibition induced by i.t. beta-endorphin (0.5-1 microgram) and DPDPE (5 micrograms) but not morphine (0.5-1 microgram), DAMGO (5 ng), norepinephrine (5 ng) or serotonin (16 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)
Tseng
L F
LF
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Collins
K A
KA
D000698:Analgesia; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*; D001615:beta-Endorphin / Q000008:administration & dosage / Q000037:antagonists & inhibitors*
D004745:Enkephalins; D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001615:beta-Endorphin; D009020:Morphine; D012844:Sincalide