T Takahashi1, Y Mizuta, C Owyang. 1. Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, USA.
Abstract
BACKGROUND & AIMS: The endogenous opiate receptor-like 1 ligand, orphanin FQ (OFQ), which structurally resembles dynorphin A, has been identified. We investigated the mechanism of action of OFQ in the colon and compared it with that of dynorphin A in vivo. METHODS: Colonic contractions were recorded via miniature force transducers implanted on the serosal surface of the rat colon. RESULTS: Intravenous administration of OFQ (0.01-3 nmol/kg) induced contractions in the rat colon in a dose-dependent manner. Colonic contractions induced by OFQ were not affected by extrinsic denervation but abolished by tetrodotoxin. Continuous infusion of OFQ (1 nmol x kg(-1) x min(-1)) and dynorphin A (100 nmol x kg(-1) x min(-1)) induced similar phasic contractions in the proximal colon. However, the contractile activity induced by the 2 peptides differed significantly in the mid and distal colon. Giant contractions induced by OFQ infusion migrated from the mid to distal colon. In contrast, dynorphin A evoked simultaneous contractions throughout the entire colon, which did not migrate aborally. Subcutaneous administration of OFQ (1-3 nmol/kg) accelerated colonic transit, whereas dynorphin A (30-100 nmol/kg) delayed colonic transit. CONCLUSIONS: The results show that OFQ accelerates colonic transit by promoting migrating colonic contractions in rats.
BACKGROUND & AIMS: The endogenous opiate receptor-like 1 ligand, orphanin FQ (OFQ), which structurally resembles dynorphin A, has been identified. We investigated the mechanism of action of OFQ in the colon and compared it with that of dynorphin A in vivo. METHODS:Colonic contractions were recorded via miniature force transducers implanted on the serosal surface of the rat colon. RESULTS: Intravenous administration of OFQ (0.01-3 nmol/kg) induced contractions in the rat colon in a dose-dependent manner. Colonic contractions induced by OFQ were not affected by extrinsic denervation but abolished by tetrodotoxin. Continuous infusion of OFQ (1 nmol x kg(-1) x min(-1)) and dynorphin A (100 nmol x kg(-1) x min(-1)) induced similar phasic contractions in the proximal colon. However, the contractile activity induced by the 2 peptides differed significantly in the mid and distal colon. Giant contractions induced by OFQ infusion migrated from the mid to distal colon. In contrast, dynorphin A evoked simultaneous contractions throughout the entire colon, which did not migrate aborally. Subcutaneous administration of OFQ (1-3 nmol/kg) accelerated colonic transit, whereas dynorphin A (30-100 nmol/kg) delayed colonic transit. CONCLUSIONS: The results show that OFQ accelerates colonic transit by promoting migrating colonic contractions in rats.