Investigation of the protective action of the E₂ prostaglandins on the gastric mucosa

The prostaglandins are found throughout the body and are therefore thought to have some physiological role. It has been suggested that prostaglandin is concerned with the maintenance of gastric mucosal integrity. In a previous study of the gastric effects of the E₂ prostaglandins, natural prostaglandin E₂ (PGE₂), 15-methyl prostaglandin E₂ (15M), and 16.16-dimethyl prostaglandin E₂ (16DM), it was observed that all three agents appeared to increase mucus production and that 16DM appeared to stimulate a non-acid secretion in basal Heidenhain pouches. These properties of the E₂ prostaglandins have been studied in detail. (Experiments 1 and 2) It has previously been shown that 15M can prevent the damaging effect of aspirin and indomethacin on the gastric mucosal barrier. Using a model in which gastric mucosal barrier damage could be produced and sustained, the ability of these agents to reverse established damage was studied. (Experiment 3) Experiment 1: The effect of topical and intravenous E₂ prostaglandins on gastric mucus production was studied in rats by measuring both the amount of mucus shed into a small volume of normal saline in the closed stomach and the amount of mucus bound to the mucosa, over a three hour period. Mucus was measured indirectly by measuring the binding of Alcian Blue. All prostaglandins caused a significant increase in the mucus found in solution, but not in that bound to the mucosa. Experiment 2: The effect of topical and intravenous administration of the three E₂ prostaglandins on non-parietal cell secretion was measured in perfused canine Heidenhain pouches. The pouches were perfused with a non-acid solution. The increase in volume was measured using polyethylene glycol as a volume marker and the HCO₃⁻ content by the method of back titration. 16DM was found to cause a significant increase in the volume, and the fluid secreted contained Na⁺, Cl⁻ and HCO₃⁻. In the absence of acid it is suggested that this represents stimulation of non-parietal cells. Experiment 3: The reversal of aspirin induced damage to the gastric mucosal barrier was demonstrated in perfused canine Heidenhain pouches. The pouches were perfused for two hours with aspirin to produce gastric mucosal barrier damage, the aspirin was then withdrawn and the pouch perfused with acid alone. The effects of topical and intravenous prostaglandins and intravenous metiamide were tested during this latter period when established barrier damage existed. Intravenous PGE₂ and 15M reversed the damage, but topical prostaglandins and intravenous metiamide did not. It is concluded that the E₂ prostaglandins have a secretory effect on the basal gastric mucosa, causing an increase in mucus production and in non-parietal cell secretion. This previously unrecognised stimulation of active secretion has lead to the misinterpretation of permeability data for 16DM. These secretory effects may have some protective action. Intravenous PGE₂ and 15M can reverse established gastric mucosal barrier damage in the dog. This indicates the possibility of a therapeutic role for these agents in the management of conditions associated with disruption of the gastric mucosal barrier.Surgery, Department ofMedicine, Faculty ofGraduat