16,16-dimethyl prostaglandin E2 (16DM) can protect the gastric mucosa from injury and yet apparently damages the gastric mucosal barrier. The effect on the gastric mucosal barrier of 16DM (26.2 micromol/l), a dose 50 times the ED50 for inhibition of acid secretion, was investigated in Heidenhain pouches in four dogs by measuring plasma shedding from the pouches after the topical application of histamine (2.7 mmol/l) and ionic fluxes. The results were compared with those using 30% ethanol, a known barrier breaker. The topical application of histamine after three hours' perfusion with 30% ethanol led to plasma shedding at a rate of 7.5 (+/-2.6) ml/h, which was significantly greater than the rate of 1.2 (+/-1.4) ml/h after three hours' perfusion with 16DM and of 1.5 (+/-1.7) ml/h in the control group. Ethanol also caused an increase in the flux of H+, Na+, and Cl-, indicating an increase in mucosal permeability, whereas 16DM increased the flux of Na+ and Cl- but not of H+. It is concluded that 16DM does not damage the gastric mucosal barrier but stimulates the secretion of fluid containing Na+ and Cl-.
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