Gastric alkaline response to mucosa-damaging agents: effect of 16,16-dimethyl prostaglandin E2.

We investigated the effects of luminal application of graded concentrations of conventional mucosal barrier breakers such as ethanol, aspirin (ASA), and sodium taurocholate (TCh), as well as 16,16-dimethyl prostaglandin E2 (DMPGE2) on gastric alkaline output (GAO) and transmucosal potential difference (PD). The Lucite chamber stomach-flap preparation was used in 50 dogs whose basal H+ secretion was inhibited by intravenous cimetidine. Graded concentrations of ethanol, and TCh at pH 5.0, and acidified solutions of ASA (at pH 5.0--2.0) were found to produce a dose-dependent increase in GAO accompanied by a stepwise decline in PD. Increasing concentrations of DMPGE2 above 1.0 microgram/ml caused a dose-related increase in GAO and a reduction in PD. The combination of DMPGE2 with ethanol aggravated the PD changes, whereas GAO induced by these agents was decreased. Alterations in GAO and PD evoked by the ASA solutions varying in pH were not significantly affected by the addition of 1.0 microgram/ml DMPGE2 to the bathing fluid. These results indicate that stimulation of gastric alkalinization with concomitant fall in PD is a common feature for various mucosa-irritant substances, and pretreatment with DMPGE2 does not prevent these effects.