Morini Giuseppina, De Caro Giuseppe, Guerrini Remo, Massi Maurizio, Polidori Carlo
Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, 43100 Parma, Italy.
Regul Pept. 2005 Jan 15;124(1-3):203-7. doi: 10.1016/j.regpep.2004.07.016.
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.
孤啡肽（Nociceptin/orphanin FQ，N/OFQ）作为NOP受体的内源性配体，对胃肠道具有多种作用。本研究旨在评估N/OFQ在维持胃黏膜完整性方面的潜在作用。在向大鼠胃内注射（灌胃）1 ml/只的乙醇（25%或50%，v/v）前30分钟，分别经中枢或外周给予N/OFQ，乙醇会造成肉眼可见的胃损伤。脑室内（i.c.v.）注射2 μg/只的N/OFQ可显著减轻由50%乙醇所致的损伤，而1 μg/只就足以显著减轻由25%乙醇所致的损伤。脑室内注射5 μg/只的选择性NOP受体拮抗剂UFP - 101，可完全逆转N/OFQ（分别为1或4 μg/只）对25%或50%乙醇损伤的保护作用。腹腔内（i.p.）注射N/OFQ可显著减轻由50%乙醇诱导的损伤，在10 μg/kg时观察到最大效应。腹腔内预先注射120 μg/kg的UFP - 101可完全消除外周注射N/OFQ的保护作用。因此，N/OFQ在中枢和外周均作为乙醇诱导的胃损伤的保护剂发挥作用，且其作用由NOP受体介导。
