Differential antagonism of U69,593- and bremazocine-induced antinociception by (-)-UPHIT: Evidence of kappa opioid receptor multiplicity in mice

摘要: The effect of pretreatment with the kappa receptor nonequilibrium antagonist, (-)-UPHIT (1S,2S-trans-2-isothiocyanato-4,5-dichloro-N-methyl-N-[2-(1-pyrrol idinyl) cyclohexyl]benzeneacetamide), on U69,593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5) dec-8-yl)benzeneacetamide]- and bremazocine-induced antinociception was examined in mice. Both bremazocine produced warm water tail-flick test after i.c.v. administration. Pretreatment nor-binaltorphimine, at doses shown not to affect [D-Ala2, NMePhe4, Gly-ol]enkephalin- (mu-agonist) or [D-Pen2, D-Pen5]enkephalin (delta-agonist)-induced antinociception, significantly attenuated effects bremazocine, suggesting actions these agonists receptors. Furthermore, beta-funaltrxamine (mu antagonist) ICI 174,864 [N,N,-diallyl-Tyr-(alpha-aminoisobutyric acid)2-Phe-Leu-OH] (delta antagonist), had no this providing further evidence receptor-mediated activity. alone a long-lasting (up 48 hr) antagonism U69,593, but antinociception. antagonist did alter antinociceptive Gly-ol]enkephalin D-Pen5]enkephalin. These data suggest that is selective, which can differentially antagonize by two agonists. provide vivo supportive subtypes mouse, may be useful probe for exploration heterogeneity.