Shuji Asada

Effects of 16, 16-dimethyl prostaglandin E2 on lysosomal membrane stability in rat stomach

The lysosomal membrane encloses numerous hydrolytic enzymes and prevents the cytoplasm from being damaged by these enzymes. It is possible that the fragility of this membrane may be implicated in the pathogenesis of gastric mucosal damage. We investigated the effects of 16,16-dimethyl prostaglandin E2 (dmPGE2), which is known to protect the gastric mucosa from various noxious agents, on lysosomal membrane stability in the rat stomach. Sodium taurocholate (TC) was used as the damaging agent. To assess lysosomal membrane stability in the gastric mucosa, we assayed acid phosphatase released from lysosomes isolated from a gastric mucosal homogenate. To assess lysosomal membrane stability in gastric surface epithelial cells, we used laser scanning confocal microscopy to observe the fading of red fluorescence in living cells vitally stained with acridine orange. Exogenous dmPGE2 enhanced lysosomal membrane stability in the gastric mucosa, whereas TC decreased it. In gastric surface epithelial cells, exogenous dmPGE2 protected the cells against TC-induced damage and prevented TC-induced decreased lysosmal membrane stability. It was concluded that a decrease in lysosomal membrane stability seemed to be closely involved in the pathogenesis of gastric mucosal damage. Moreover, it appears that stabilization of the lysosomal membrane by exogenous dmPGE2 may contribute to its protective effect in the gastric mucosa, both at the level of gastric surface epithelial cells and in regard to the entire gastric mucosa.

Effects of anti-acid secretory agents on various types of gastric mucus.

Total, acidic, and sulfated mucus contents in the gastric mucosa were evaluated after administration to rats of ranitidine and pirenzepine, antagonists of gastric parietal cell receptors; omeprazole, a proton-pump/inhibitor; and misoprostol, a prostaglandin E1 preparation. Total gastric mucus content was significantly decreased by ranitidine, but contents of acidic mucus and sulfated mucus showed a slight increase. Total mucus and acidic mucus contents were slightly increased after administration of pirenzepine, whereas the sulfated mucus content was significantly increased. The total gastric mucus content was significantly decreased after administration of omeprazole, but acidic mucus increased slightly and sulfated mucus increase significantly. All mucus contents were unchanged after administration of anti-acid secretory dose of midoptodyol. After administration of either ranitidine or omeprazole, the neutral mucus content decreased, but the total acid and sulfated mucus contents were not decreased. Changes in various mucus contents following inhibition of acid secretion are different for different drugs, and it was suggested that production of neutral mucus and secretion of acid mucus were reduced by strong inhibition of acid secretion.

Correlation of gastric mucous volume with levels of five prostaglandins after gastric mucosal injuries by NSAIDs.

After administration of NSAIDs (aspirin and indomethain), chronological changes in gastric mucous volume were etermined. These mucous volume changes were evaluated n relation to the development of gastric mucosal injuries. urthermore, quantitative changes in five kinds of prostalandins (PGs) in the gastric mucosa were measured after dministration of NSAIDs. Gastric mucus volume was easured using a video image processor (VIP), and five cinds of PCs were fractionated by high-performance liquid hromatography (HPLC) and quantitatively determined by adioimmunoassay (RIA). We found that NSAIDs decrease he levels of five kinds of PGs to the same extent. Also, astric mucous volume is decreased after administration of spirin and increased after administration of indomethain. Accordingly, it is possible that each NSAID has a different mechanism of producing the gastric mucosal injury nd acts on gastric mucus in a different manner. There was o parallel in changes between gastric mucous volume and G levels of the different PGs in the gastric mucosa after dministration of NSAIDs.