Loop-diuretic inhibition of adrenaline-stimulated Cl- secretion in a cultured epithelium of renal origin (MDCK).

Loop diuretics (furosemide, bumetanide, piretanide) inhibit the adrenaline-stimulated short-circuit current due to transepithelial Cl- secretion in cultured renal epithelial layers (MDCK). The inhibition of Cl- secretion by loop diuretics is consistent with the presence of basal-lateral 'cotransport' since inhibition is observed only with the basal applications of loop diuretics, is of high potency (half-maximal bumetanide inhibition being observed at 0.8 microM, bumetanide being more potent than furosemide) and is without effect upon the adrenaline-stimulated increase in tissue conductance. Loop diuretics are also shown to inhibit a component of K+ efflux across the basal-lateral surfaces. Cellular uptake of [3H]bumetanide across both apical and basal surfaces of intact epithelial layers was measured in order to localize the cotransport system. A component of cellular [3H]bumetanide uptake sensitive to competition by 0.1 mM unlabelled loop diuretic is only observed from the basal-lateral cell surfaces. There is no evidence for transepithelial bumetanide secretion as is seen in renal cortex.