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 4h 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 microg/kg/h i.p. Its effect was reversed by the selective NOP receptor antagonist [Nphe(1)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-101), 30 microg/kg/h ip. The selective NOP receptor agonist [(pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-112), 0.01-0.3 microg/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.
Grandi
Daniela
D
Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, Via Volturno 39, I-43100 Parma, Italy.
Solenghi
Elvira
E
Guerrini
Remo
R
Polidori
Carlo
C
Massi
Maurizio
M
Morini
Giuseppina
G
D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D012149:Restraint, Physical / Q000009:adverse effects; D013312:Stress, Physiological / Q000150:complications / Q000378:metabolism; D000094942:Nociceptin Receptor
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C466980:nociceptin orphanin FQ(1-17)OH; C000722285:Oprl1 protein, rat