Peripheral mechanisms involved in gastric mucosal protection by intracerebroventricular and intraperitoneal nociceptin in rats.
Nociceptin (N/OFQ) exerts multiple effects in the gastrointestinal tract after central or peripheral administration. In the present study, we examined the possible peripheral mechanisms mediating gastric protection by N/OFQ in rats. Gastric mucosal lesions were induced by 50% ethanol (1 ml/rat intragastrically). N/OFQ, administered either intracerebroventricularly (3 microg/rat) or ip (10 microg/kg), significantly reduced macroscopic and histological damage. The protective effect of intracerebroventricular N/OFQ was blocked by atropine, subdiaphragmatic vagotomy, and bretylium. The effect of both central and peripheral N/OFQ was blocked by functional ablation of afferent nerves produced by capsaicin, by the antagonist of calcitonin gene-related peptide, CGRP(8-37), and by the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester. These results indicate that N/OFQ increases gastric mucosal resistance to ethanol by operating both in the central nervous system and in the periphery. Vagal cholinergic and sympathetic pathways mediate the central activity of N/OFQ, whereas vagal nonmuscarinic pathways mediate the peripheral activity of the peptide. The neuronal circuit involving extrinsic sensory neurons, calcitonin gene-related peptide, and nitric oxide is activated by central as well as peripheral N/OFQ. The study provides evidence that N/OFQ contributes to neurally mediated gastric mucosal protection.
Polidori
Carlo
C
Department of Experimental Medicine and Public Health, University of Camerino, Italy.
Massi
Maurizio
M
Guerrini
Remo
R
Grandi
Daniela
D
Lupo
Daniela
D
Morini
Giuseppina
G
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001949:Bretylium Compounds / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D018738:Hexamethonium / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008916:Miotics / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D018847:Opioid Peptides / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology; D014628:Vagotomy; D000097629:Nociceptin
D000889:Anti-Arrhythmia Agents; D001285:Atropine; D001949:Bretylium Compounds; D015740:Calcitonin Gene-Related Peptide; D002492:Central Nervous System Depressants; D000431:Ethanol; D005730:Ganglionic Blockers; D018738:Hexamethonium; D008916:Miotics; D009569:Nitric Oxide; D018847:Opioid Peptides; D010276:Parasympatholytics; D010446:Peptide Fragments; D000097629:Nociceptin; C058636:calcitonin gene-related peptide (8-37); C045166:bretylium