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

Abstract

ABSTRACT-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 pro tective effect of 0.2 N HCl more strongly than that of 0.35 N HCI, both of which markedly inhibited HCI ulcer. lV°-Nitro-L-arginine (L-NNA) did not affect the protective effect afforded by either 0.2 N HCl or 0.35 N HCI. Combined pretreatment with indomethacin and L-NNA did not diminish the protective action induced by 0.35 N HCI, 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 HCI; 3) In the case of 0.35 N HCI, 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 cyto protection.

Effects of endotoxin on gastric injury from luminal irritants in rats: potential roles of nitric oxide

“…These observations would seem to imply that induction of this enzyme represents a mechanism of local intestinal damage. This being the case, one possible interpretation of the data reported by Tepperman and Soper (24) is that LPS causes mild irritation to the gastric mucosa through induction of iNOS and thereby elicits an adaptive cytoprotective response in the stomach (8,28). However, Ferraz et al (7) recently reported that endotoxin pretreatment enhanced the susceptibility of the stomach to damage and that this effect was negated by NOS inhibition with aminoguanidine, which is more selective for iNOS.…”

Central and peripheral vagal mechanisms involved in gastric protection against ethanol injury

“…In addition to PG, the activation of the efferent function of capsaicin‐sensitive splanchnic afferents leading to a CGRP–NO‐dependent increase in gastroprotective vasodilatory mechanisms has been identified pharmacologically and biochemically. Medullary TRH is involved in the vagal‐dependent adaptive gastric protection induced by intragastric pretreatment with low acid or EtOH, as shown by the use of TRH antibody injected into the DVC and the similarity of peripheral transmitters mediating central TRH and adaptive gastric protection 75 . Other specific neuropeptides, such as PYY, somatostatin analogues and members of the CGRP family, also act centrally to protect gastric mucosa against EtOH injury through vagal pathways involving PG, CGRP, NO and/or VIP (Table 1).…”

Central and peripheral vagal mechanisms involved in gastric protection against ethanol injury

“…Medullary TRH is involved in the vagal-dependent adaptive gastric protection induced by intragastric pretreatment with low acid or EtOH, as shown by the use ofTRH antibody injected into the DVC and the similarity of peripheral transmitters mediating central TRH and adaptive gastric protection. 75 Other specific neuropeptides, such as PYY, somatostatin analogues and members of the CGRP family, also act centrally to protect gastric mucosa against EtOH injury through vagal pathways involving PG, CGRP, NO and/or VIP (Table 1).…”