Antagonistic effects of CompB on orphanin FQ-induced colonic contractions in rats.

摘要

Orphanin FQ has been shown to stimulate colonic contraction without affecting upper gastrointestinal motility in rats. We studied whether a new putative orphanin FQ receptor antagonist, 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one (CompB), has antagonistic effects on orphanin FQ-induced colonic contractions in vivo and in vitro in rats. Orphanin FQ-(1-17) and orphanin FQ-(1-13) caused contractions of the circular muscle of the distal colon in a concentration dependent manner (10(-10)-10(-6) M) in vitro. CompB (10(-7)-10(-6) M) caused a significant inhibition on orphanin FQ-(1-17) and orphanin FQ-(1-13)-induced contractions without affecting the spontaneous contractions. Orphanin FQ-(1-17) also caused contractions of the distal colon in vivo. ED(50) dose of orphanin FQ-(1-17) (400 pmol/kg)-induced contractions were significantly antagonized by CompB (30-300 nmol/kg) in a dose-dependent manner. In contrast, CompB had no inhibitory effects on dynorphin A-induced contractions in vivo and in vitro. These indicate that CompB is a selective orphanin FQ receptor antagonist of the rat colon.