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-i nduced antinociception in diabetic mice. Endomorphin-1 (1-10 mug, i.c.v.) a nd endomorphin-2 (3-30 mug, i.c.v.) dose dependently inhibited the tail-fli ck response in non-diabetic and diabetic mice. There was no significant dif ference between the antinociceptive effect of endomorphin-1 in non-diabetic and diabetic mice. On the other hand, the antinociceptive effect of endomo rphin-2 in diabetic mice was significantly less than that in non-diabetic m ice. Cholecystokinin octapeptide (CCK-8) dose dependently reduced the antin ociceptive effects of endomorphin-1 and endomorphin-2 in non-diabetic mice. However, in diabetic mice, CCK-8 significantly inhibited the antinocicepti ve 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-oxybuta noic acid) had no significant effect on either endomorphin-1- or endomorphi n-2-induced antinociception. In diabetic mice, while CI-988 had no signific ant effect on endomorphin-1-induced antinociception, it dose dependently en hanced the antinociceptive effect of endomorphin-2. The results indicated t hat the reduction of endomorphin-2-induced antinociception in diabetic mice might be due, at least in part, to the activation of CCK2 receptors. (C) 2 001 Published by Elsevier Science B.V.