Acid pH and weak acids induce Na--Cl cotransport in the rabbit urinary bladder.
We have described a coupled Na--Cl entry step at the apical membrane of a tight epithelium, the rabbit urinary bladder. Mucosal pH values, more acid than 4.6, stimulate a 20 to 40-fold increase in mucosal-to-serosal Na+ and Cl- flux. The flux increase is almost completely blocked by low concentrations of of bumetanide. The transepithelial movement of Na+ and Cl- is normally electroneutral; however, when weak acids (such as acetate) are present in the mucosal solution, the acid-induced increase in flux is accompanied by a large increase in short-circuit current. Besides blockage by bumetanide, both the increase in flux and short-circuit current are blocked by: (1) Na+-free solutions on the mucosa; (2) Cl--free solutions on the mucosa; (3) phosphodiesterase inhibitors; (4) ouabain in the serosal solution; (5) K+-free solutions on the serosa; and (6) HCO3--free solutions on the serosa. The increase in the fluxes and the short-circuit current is unaffected by: (1) amiloride application in the mucosal solution; (2) mucosally applied stilbene derivatives which block Cl-/HCO3- exchange (SITS); and (3) Cl--free solutions applied to the serosa. We interpret these results to imply a coupled Na--Cl uptake step at the apical membrane which is stimulated by intracellular acetate (or (pH). The uptake step leads to a movement of Na+ and Cl- across the basolateral membrane, which is mediated by the Na+, K+-ATPase and a Na/Cl/HCO3- exchange mechanism. Our results demonstrate that "tight" epithelia may, under appropriate circumstances, demonstrate mechanisms of ion movement which are similar to "leaky" epithelia.
D000143:Acids / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*
D000143:Acids; D002712:Chlorides; D002034:Bumetanide; D010042:Ouabain; D000584:Amiloride; D012964:Sodium