Orphanin FQ, but not dynorphin A, accelerates colonic transit in rats.
OBJECTIVE
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.
Takahashi
T
T
Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, USA.
Mizuta
Y
Y
Owyang
C
C
D000818:Animals; D003106:Colon / Q000187:drug effects*; D004399:Dynorphins / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007422:Intestines / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects; D013997:Time Factors; D000097629:Nociceptin
D004399:Dynorphins; D018847:Opioid Peptides; D000097629:Nociceptin