Nociceptin/orphanin FQ prevents gastric damage induced by cold-restraint stress in the rat by acting in the periphery

The influence of peripheral nociceptin/orphanin FQ (N/OFQ) on cold restraint-induced gastric mucosal damage in the rat was investigated. Exposure to cold-restraint for 3 and 4 h caused the formation of hemorrhagic lesions in the glandular portion of the stomach. N/OFQ dose-dependently decreased lesion formation, in the range 0.03-1 μg/kg/h i.p. Its effect was reversed by the selective NOP receptor antagonist [Nphe1Arg14Lys15]N/OFQ-NH2 (UFP-101), 30 μg/kg/h ip. The selective NOP receptor agonist [(pF)Phe4Aib7Arg14Lys15]N/OFQ-NH2 (UFP-112), 0.01-0.3 μg/kg/h i.p., similarly reduced lesion formation. Light and scanning electron microscopy confirmed the protective activity of N/OFQ. Cold-restraint stress causes a reduction in mucus content and in adhering mucus layer, partly counteracted by N/OFQ. These results suggest that N/OFQ counteracts acute stress-induced gastric mucosal damage by interacting with NOP receptor and by influencing mucous cell activity.