Nociceptin/orphanin FQ prevents ethanol-induced gastric lesions in the rat.
Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP receptor, exerts a variety of effects on the gastrointestinal tract. The present study was aimed at evaluating the possible implication of N/OFQ in the maintenance of gastric mucosal integrity. N/OFQ was given either centrally or peripherally 30 min prior to intragastric administration (i.g.) of 1 ml/rat of ethanol (either 25% or 50%, v/v), which produces macroscopically visible gastric lesions. Intracerebroventricular (i.c.v.) injection of 2 microg/rat of N/OFQ significantly reduced lesions caused by 50% ethanol, while 1 microg/rat was enough to significantly reduce lesions caused by 25% ethanol. Intracerebroventricular injection of 5 microg/rat of the selective NOP receptor antagonist, UFP-101, completely reversed the protective effect of N/OFQ, 1 or 4 microg/rat against 25% or 50% ethanol, respectively. The intraperitoneal (i.p.) injection of N/OFQ produced a significant reduction of lesions induced by 50% ethanol, the peak effect being observed at 10 microg/kg. Intraperitoneal pretreatment with UFP-101, 120 microg/kg, completely abolished the protective effect of peripherally injected N/OFQ. Therefore, N/OFQ acts both centrally and peripherally as a protective agent against ethanol-induced gastric lesions, and its effect is mediated by NOP receptors.
Morini
Giuseppina
G
Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, 43100 Parma, Italy.
De Caro
Giuseppe
G
Guerrini
Remo
R
Massi
Maurizio
M
Polidori
Carlo
C
D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D018847:Opioid Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D000097629:Nociceptin
D000431:Ethanol; D018847:Opioid Peptides; D000097629:Nociceptin