Slomiany A

Enhancement in the protective qualities of gastric mucus by ebrotidine during duodenal ulcer healing

1. Gastric mucus from duodenal ulcer patients before and following therapy with a new antiulcer agent, ebrotidine, at 400, 600 and 800 mg dose was examined for changes in the physicochemical qualities and anti-H. pylori activity. 2. The results of physical measurements revealed that successful therapy with ebrotidine was accompanied by a 25% increase in gastric mucus viscosity, and a 20% increase in H+ retardation capacity, while its hydrophobicity increased by 11%. 3. The enhancement in the physical properties of mucus with ebrotidine therapy were also reflected in a marked (2.6-2.9-fold) increase in the proportion of the high molecular weight form of mucin. Furthermore, following therapy with ebrotidine, the gastric mucins showed a 36% higher content of sulfate as compared to that before the therapy. 4. Assays on the H. pylori aggregating titer of gastric mucin revealed that ebrotidine therapy at all three doses evoked a 4-fold increase in mucin anti-H. pylori activity. 5. The data demonstrate that duodenal ulcer therapy with ebrotidine leads to a marked improvement in the protective qualities of gastric mucus essential for the maintenance of mucosal integrity and enhances the inherent mucosal defense against H. pylori infection.

Enhancement of gastric mucus phospholipid secretion by an antiulcer agent, ebrotidine.

1. Rat gastric mucosal cells, subjected to phospholipid labeling by incubating the cell suspension in DMEM with [3H]choline, were exposed to different concentrations (0-150 microM) of H2-receptor antagonists, ebrotidine and ranitidine, and the phospholipid secretory responses were evaluated. 2. In the absence of the drugs, the secretion of choline-containing phospholipids over a 1 hr period averaged 3.97% of the total cellular labeled phospholipids. Ebrotidine caused a dose-dependent increase in the rate of phospholipid secretion which was most pronounced at 1 hr and persisted for at least 2 hr. The maximal effect was attained at 120 microM ebrotidine giving a 36% increase in phospholipid secretion. 3. The phospholipid secretory response to ebrotidine was accompanied by an increase in gastric mucosal cell cAMP level which reached a maximum value of 2.1-fold over that of controls at 1 hr. Ranitidine, in contrast, neither evoked increase in cAMP level nor caused any stimulation in phospholipid secretion. 4. The results indicate that the gastroprotective properties of ebrotidine are associated with the ability of the drug to elicit a rapid stimulation in gastric mucus phospholipid secretion, and that ranitidine does not possess such property.