Effect of inhibitors on transepithelial efflux of Na and nonelectrolytes in frog skin.

The transepithelial efflux of Na and several nonelectrolytes (mannitol, sucrose, and polyethylene glycol 900) were measured in the isolated frog skin under short-circuited conditions in chambers that had been specially designed to avoid edge damage. Ouabain (10(-3) and 10(-4) M) caused a dramatic increase in the efflux of Na, whereas the efflux of nonelectrolytes showed only a slight alteration. The efflux of Na increased after the application of dinitrophenol (10(-4) M), whereas the efflux of nonelectrolytes remained constant. Amiloride (10(-3) M) caused large variations in the efflux of Na, whereas the efflux of nonelectrolytes remained unchanged. The results provide evidence that these inhibitors do not alter the permeability of the paracellular pathway and that the total transepithelial efflux of Na or at least a very large portion of it, and possibly also the transepithelial efflux of Cl, proceeds via a transcellular pathway and not a paracellular pathway as has been widely accepted. The data further suggest that the Na proceeding via this pathway interacts directly or indirectly with the active transport step.