Effect of barrier-breaking agents on intracellular pH and epithelial membrane resistances: studies in isolated Necturus antral mucosa exposed to luminal acid.

Features of "H+ back-diffusion" after disruption of the gastric mucosal barrier were investigated by assessing, with a microelectrode technique, the influence of three barrier-breaking agents, taurocholate (10 mM), ethanol (20% vol/vol), and acetylsalicylic acid (10 mM) on intracellular pH and epithelial membrane potentials and resistances in isolated Necturus antral mucosa exposed to luminal acid (pH 3). Exposure of the mucosa to each of the three agents induced intracellular acidification of surface epithelial cells, but the pattern of pHi behavior was different for each agent: taurocholate induced immediate acidification of pHi, ethanol acidified pHi after a delay of 4-6 min, whereas acetylsalicylic acid initially alkalinized pHi, whereafter a rapid acidification of pHi occurred. Assessment of intraepithelial membrane resistances indicated that taurocholate primarily increases cellular conductance, decreasing in particular Ra. In contrast, ethanol mainly increased paracellular conductance, but also decreased cellular resistance, in particular Ra. Acetylsalicylic acid initially increased cell membrane resistances and Ra/Rb, whereafter a rapid decrease of Ra/Rb and Rt occurred. In each instance, the decrease of Ra/Rb preceded acidification of pHi. The data suggest that all three agents induce intracellular acidification by increasing the conductance of the apical cell membrane to H+, but in ethanol-treated tissues paracellular conductance primarily contributes to H+ back-diffusion.