2002 Volume 120 Issue 1 Pages 21-28
The gastric mucosa responds to damaging agents by decreasing acid secretion (luminal alkalinization), together with increase in mucosal prostaglandin (PG) content and luminal release of nitric oxide (NO), histamine and Ca2+. The acid inhibitory mechanism in the damaged stomach involves endogenous NO as well as PG, and the acid secretion turns into “stimulation” only in the presence of NG-nitro-L-arginine methyl ester (L-NAME) but not aminoguanidine. The acid stimulation caused by L-NAME in the damaged stomach is mediated by endogenous histamine released from mucosal mast cells, the process being inhibited by a mast cell stabilizer and chelation of luminal Ca2+ as well as sensory deafferentation and also facilitated by PG. The acid and PG biosynthetic responses in the damage stomach are inhibited by SC-560 the selective cyclooxygenase (COX)-1 inhibitor but not rofecoxib the selective COX-2 inhibitor. Thus, damage in the gastric mucosa enhances the acid stimulatory pathway in addition to the COX-1/PG and cNOS/NO-mediated inhibitory pathways, although the latter effect normally overcomes the former, resulting in a decrease of acid secretion. Since luminal alkalinization caused by a decrease of acid secretion contributes to maintenance of the miroclimate for cellular restitution, this response is physiologically important for tissue recovery from injury.
