Effect of aldosterone and insulin on mannitol, Na+ and Cl- fluxes in cultured epithelia of renal origin (A6): evidence for increased permeability in the paracellular pathway.

Transepithelial fluxes of mannitol, Na+ and Cl- were measured under open circuit conditions in cultured epithelia derived from toad kidney (A6). Both aldosterone and aldosterone plus insulin produced significant increases in the apparent permeability to mannitol (40 and 83%, respectively). Na+ permeabilities calculated from basolateral to apical Na+ fluxes showed approximately the same percentage increases in response to aldosterone and aldosterone plus insulin. Cl- permeabilities calculated from basolateral to apical Cl- fluxes did not show the same percentage increases. The flux ratios for Cl- were significantly lower than would be predicted for simple electrochemical diffusion in both control and hormone-treated epithelia. In aldosterone-treated epithelia, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) caused Cl- flux ratios to approach predicted values. The unidirectional Cl- fluxes may have significant contributions from both the transcellular and paracellular pathways, with the direction of departure from predicted values being consistent with the presence of Cl- exchange diffusion. In aldosterone plus insulin-treated epithelia, amiloride significantly reduced both the mannitol and Na+ permeabilities. These findings are consistent with aldosterone- and aldosterone plus insulin-induced increases in paracellular pathway permeability which may be secondary to the change in active Na+ transport rather than a primary effect.