Multiple Mediators and Mechanisms Are Involved in the Adaptive Cytoprotection Provided by Certain Mild Irritants

• Published in: Japanese Journal of Pharmacology Vol. 63; no. 2; pp. 251 - 256
• Main Authors: Hatakeyama, Yoshifumi, Matsuo, Masahiko, Tomoi, Masaaki, Mori, Jo, Kohsaka, Masanobu
• Format: Journal Article
• Language: English; Japanese
• Published: Kyoto The Japanese Pharmacological Society 1993; Japanese Pharmacological Society
• Subjects: Adaptive cytoprotection; Animals; Arginine; Arginine - analogs & derivatives; Arginine - pharmacology; Biological and medical sciences; Digestive system; Gastric Mucosa - drug effects; Indomethacin - pharmacology; Irritants - pharmacology; Male; Medical sciences; Mild irritant; Nitric oxide; Nitric Oxide - pharmacology; Nitroarginine; Pharmacology. Drug treatments; Prostaglandin; Prostaglandins - pharmacology; Rats; Rats, Sprague-Dawley; Stomach Ulcer - chemically induced; Stomach Ulcer - prevention & control; Mild irritant; Adaptive cytoprotection; Arginine; Prostaglandin; Nitric oxide; Stomach; Rat; Arachidonic acid derivatives; Rodentia; Base; Mechanism; Prevention; Vertebrata; Mammalia; Acids; Cytoprotector; Animal; Nitrogen monoxide; Digestive diseases; Irritant compound; Lesion; Adaptive modulation; Gastric disease
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.63.251

We investigated the participation of prostaglandins (PG) and nitric oxide (NO) in adaptive cytoprotection using 0.6 N HCl-induced gastric lesions in the rat stomach. Indomethacin reversed the protective effect of 0.2 N HC1 more strongly than that of 0.35 N HC1, both of which markedly inhibited HC1 ulcer. NG-Nitro-L-arginine (L-NNA) did not affect the protective effect afforded by either 0.2 N HC1 or 0.35 N HC1. Combined pretreatment with indomethacin and L-NNA did not diminish the protective action induced by 0.35 N HC1, but almost completely abolished the indomethacin-resistant protection afforded by 0.1 N NaOH. Acid mild irritant increased the gastric fluid volume concentration-dependently, whereas alkaline mild irritant had little or no effect on the volume. These results suggest that: 1) The mediators involved in adaptive cytoprotection afforded by 0.1 N NaOH may be fully ascribed to PG and NO; 2) PG is a major mediator in the protection induced by 0.2 N HC1; 3) In the case of 0.35 N HC1, the mediators remain to be determined since increased gastric fluid volume could contribute to the protection through dilution. These findings thus may indicate that multiple mediators and mechanisms are implicated in adaptive cytoprotection.