Role of cholecystokinin in the reduction of endomorphin-2-induced antinociception in diabetic mice.
We examined the role of cholecystokinin in the reduction of endomorphin-2-induced antinociception in diabetic mice. Endomorphin-1 (1-10 microg, i.c.v.) and endomorphin-2 (3-30 microg, i.c.v.) dose dependently inhibited the tail-flick response in non-diabetic and diabetic mice. There was no significant difference between the antinociceptive effect of endomorphin-1 in non-diabetic and diabetic mice. On the other hand, the antinociceptive effect of endomorphin-2 in diabetic mice was significantly less than that in non-diabetic mice. Cholecystokinin octapeptide (CCK-8) dose dependently reduced the antinociceptive effects of endomorphin-1 and endomorphin-2 in non-diabetic mice. However, in diabetic mice, CCK-8 significantly inhibited the antinociceptive effect of endomorphin-1, but not of endomorphin-2. In non-diabetic mice, CI-988 ((R-[R*,R*])-4-([3-1H-indol]-3-yl)-2-methyl-1-oxo-2-([(tricyclo(3.3.1.1)dec-2-yloxy)carbonyl] amino)propylamino-1-phenyl-ethylamino-4-oxybutanoic acid) had no significant effect on either endomorphin-1- or endomorphin-2-induced antinociception. In diabetic mice, while CI-988 had no significant effect on endomorphin-1-induced antinociception, it dose dependently enhanced the antinociceptive effect of endomorphin-2. The results indicated that the reduction of endomorphin-2-induced antinociception in diabetic mice might be due, at least in part, to the activation of CCK(2) receptors.
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa, 142-8501, Tokyo, Japan. kamei@hoshi.ac.jp
J
J
Kamei
K
K
Zushida
H
H
Nagase
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009619:Nociceptors / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010146:Pain / Q000517:prevention & control*; D010147:Pain Measurement; D012844:Sincalide / Q000494:pharmacology
D000700:Analgesics; D007211:Indoles; D009842:Oligopeptides; C105293:endomorphin 1; C065599:PD 134308; C105294:endomorphin 2; D008536:Meglumine; D002766:Cholecystokinin; D012844:Sincalide