Ionic fluxes induced by topical misoprostol in canine gastric mucosa

Abstract

We studied the dose response of ionic fluxes in canine chambered gastric segment mucosa to increasing doses of topical misoprostol (0.1, 1, 10, 100, and 1000 μg). The fluxes were also correlated with the simultaneous changes in focal gastric mucosal blood flow measured by laser–Doppler flowmetry. After misoprostol administration, there was a dose-dependent increase in focal gastric mucosal blood flow (Emax = 8.23 ± 3.25 V at 10 μg; ED50 = 1.05 μg),pH, and the outputs of ions (Na+, K+, Cl−, and HCO3−) and fluid (Emax for pH and fluxes ≥ 1000 μg). ED50 values for these outputs ranged from 215.40 to 340 μg (mean ± SE = 279.08 ± 24.27 μg). H+ output showed a dose-dependent decrease to zero at the 10-μg dose, the dose at and after which net HCO3− secretion became obvious. The slopes of the dose–response curves for the fluxes of fluid, Na+, K+, Cl−, and HCO3− were significantly different (p < 0.01) from the slope of the curve for mucosal blood flow changes. There were no correlations between the changes in these fluxes and blood flow changes. Na+ and Cl− were the predominant cation (98.84%) and anion (98.19%), respectively, in the misoprostol-induced secretion. Misoprostol stimulates a composite alkaline gastric nonparietal secretion, predominantly Na+ and Cl−, but also containing K+ and HCO3−. Our results suggest different mechanisms for the effects on nonparietal secretion and focal gastric mucosal blood flow. ED50 values for the effects on ionic–fluid fluxes were in the antisecretory dose range,while that for mucosal blood flow changes was in the cytoprotective range.Key words: nonparietal secretion, prostaglandin E1; mucosa, blood flow, stomach.