Peripheral and central actions of orphanin FQ (nociceptin) on murine colon

Abstract

Orphanin FQ (OFQ), also known as nociceptin, is a recently isolated endogenous peptide with a structure similar to the endogenous opioid peptides. The present study examines the actions of centrally administered OFQ on in vivo murine gastrointestinal and colonic transit as well as the actions of OFQ on the isolated colon. Intracerebroventricular injections of OFQ dose dependently inhibited colonic propulsive activity. OFQ inhibition of colonic propulsion was unaffected by coadministration of the competitive opioid receptor antagonist naltrexone. A subadditive response was observed when approximately equipotent doses of either morphine sulfate or the δ-agonist DPDPE were coadministered with OFQ. No subadditivity was observed with coadministration of the μ-agonist DAMGO, suggesting a functional interaction between OFQ and δ-opioid central pathways regulating colonic transit. High, but not low, doses of OFQ also inhibited the transit of a nonabsorbable charcoal marker through the stomach and/or small intestine. OFQ potently contracted isolated colon preparations; contractile activity was abolished by TTX or chlorpromazine. Our results suggest that OFQ may be an important peptide ligand acting on a novel inhibitory neural pathway that modulates gastrointestinal transit.

[Arg14,Lys15]Nociceptin, a Highly Potent Agonist of the Nociceptin/Orphanin FQ Receptor: in Vitro and in Vivo Studies

“…1). The effects of the NC analog were also tested in other preparations, such as the guinea pig ileum and rat vas deferens, in which NC inhibits the twitch response to electrical field stimulation , and in the mouse colon, in which NC induces concentration-dependent contractions (Osinski et al, 1999). In all these tissues, [Arg 14 ,Lys 15 ]NC elicited similar maximal effects to NC but displayed higher potency by 5-fold in the guinea pig ileum and mouse colon and by 10-fold in the rat vas deferens (Table 1).…”

Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters

“…The motility of the colon was evaluated in separate sets of control and SERT Ϫ/Ϫ littermates. Animals were lightly anesthetized with ether, and a glass microbead (3 mm in diameter) was inserted through the anus and pushed, with a polished glass rod, into the colon for a distance of 2 cm (Osinki et al, 1999). The time from the completion of insertion to the expulsion of the bead was measured to the nearest 0.1 min to provide an estimate of the rate of transit in the colon.…”

Nociceptin effect on intestinal motility depends on opioid-receptor like-1 receptors and nitric oxide synthase co-localization

“…No other structures apart from neurons appear to be stained. results are often contradictory, depending on the site of administration, dose used and the animal model employed in the study [23,26,35,36] . Our observations in vivo clearly showed a differential, ORL1-dependent action of nociceptin in the mouse ileum and colon, where it accelerates and decreases the intestinal motility, respectively.…”