Functional significance of a newly discovered neuropeptide, orphanin FQ, in rat gastrointestinal motility

Background & Aims: Orphanin FQ (OFQ) is a recently discovered neuropeptide that structurally resembles an opioid peptide. However, the functional role of OFQ in rat gastrointestinal tract remains unknown, Methods: We investigated the effects of OFQ on contractions of muscle strips obtained from different regions of the gastrointestinal tract. Immunohistochemical studies were performed on rat colonic tissue using OFQ antibody. Results: OFQ (10(-9) to 10(-7) mol/L) caused significant contractions in the rat colon but not in the stomach or small intestine. Tetrodotoxin, veratridine, and long-term serosal application of benzalkonium chloride completely abolished OFQ-induced colonic contractions without affecting myogenic contractions in response to carbachol, OFQ-induced contractions were not affected by naloxone, atropine, phentolamine, propranolol, methysergide, substance P antagonist, vasoactive intestinal polypeptide antagonist, apamin, and N-G-nitro-L-arginine methyl ester, OFQ (10(-9) to 10(-7) mol/L) significantly reduced muscle contractions and H-3-acetylcholine release in response to electrical field stimulation in both the stomach and small intestine but not in the colon, OFQ-immunopositive neuronal fibers were found in the colonic myenteric plexus. Conclusions: These studies indicate that the mechanisms and sites of action of OFQ are region specific. OFQ inhibits cholinergic transmission in the stomach and small intestine, whereas OFQ stimulates colonic contraction possibly by inhibiting an inhibitory neural pathway within the myenteric plexus.