LOOP-DIURETIC INHIBITION OF ADRENALINE-STIMULATED Cl- SECRETION IN A CULTURED EPITHELIUM OF RENAL ORIGIN (MDCK)

• Published in: Experimental physiology 1986-04, Vol.71 (2), p.183-193
• Main Authors: Brown, C. D. A., Rugg, E. L., Simmons, N. L.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bumetanide - metabolism; Bumetanide - pharmacology; Cell Line; Cell physiology; Chlorides - antagonists & inhibitors; Chlorides - secretion; Diuretics - pharmacology; Dogs; Electrophysiology; Epinephrine - pharmacology; Epithelium - metabolism; Fundamental and applied biological sciences. Psychology; Furosemide - pharmacology; Kidney - cytology; Kidney - drug effects; Kidney - metabolism; Kidney - physiology; Membrane and intracellular transports; Molecular and cellular biology; Potassium - metabolism; Radioisotopes; Rubidium - metabolism; Stimulation, Chemical; Sulfonamides - pharmacology
• ISSN: 0958-0670; 0144-8757; 1469-445X
• DOI: 10.1113/expphysiol.1986.sp002977

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 µM, 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 [ 3 H]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.