, Volume 61, Issue 20, pp 1019-1027

Cellular mechanism of the action of loop diuretics on the thick ascending limb of Henle's loop

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Summary

During the passed few years the cellular mechanisms responsible for the NaCl reabsorption in the thick ascending limb of the Henle loop of mammalian nephron and of the early distal tubule of amphibian kidney have been extensively studied. From these studies a new type of secondarily active transport mechanism, i.e. the Na+ - 2Cl - K+ symport has emerged. Meanwhile it has been recognized that this system is also present in many other epithelia. All these epithelia share in common that they are sensitive to the so called loop diuretics. The present article summarizes our current knowledge of how the loop diuretics, by reversible interaction with the above cotransport system, inhibit the NaCl reabsorption in the thick ascending limb of Henle's loop. It is shown that these drugs transfer the thick ascending limb cell to a state in which not only transepithelial NaCl reabsorption ceases but in which also very little energy is consumed since then K+ and Cl “relax” to passive distribution across both cell membranes and Na+ entry into the cell is blocked.

Supported by Deutsche Forschungsgemeinschaft: Gr 480/5-7