Orphanin FQ, but not dynorphin A, accelerates colonic transit in rats

Background & Aims: The endogenous opiate receptor-like 1 ligand, orphanin F Q (OFQ), which structurally resembles dynorphin A, has been identified. We investigated the mechanism of action of OFQ in the colon and compared it wi th that of dynorphin A in vivo, Methods: Colonic contractions were recorded via miniature force transducers implanted on the serosal surface of the ra t colon. Results: Intravenous administration of OfQ (0.01-3 nmol/kg) induce d contractions in the rat colon in a dose-dependent manner. Colonic contrac tions induced by OfQ were not affected by extrinsic denervation but abolish ed by tetrodotoxin, Continuous infusion of OFQ (1 nmol . kg(-1) . min(-1)) and dynorphin A (100 nmol . kg(-1) . min(-1)) induced similar phasic contra ctions in the proximal colon. However, the contractile activity induced by the 2 peptides differed significantly in the mid and distal colon. Giant co ntractions induced by OFQ infusion migrated from the mid to distal colon. I n contrast, dynorphin A evoked simultaneous contractions throughout the ent ire colon, which did not migrate aborally. Subcutaneous administration of O FQ (1-3 nmol/kg) accelerated colonic transit, whereas dynorphin A (30-100 n mol/kg) delayed colonic transit, Conclusions: The results show that OFQ acc elerates colonic transit by promoting migrating colonic contractions in rat s.