[The loop diuretic bumetanide as a tool in physiology and pharmacology]

Loop diuretics are derivatives of 4-sulfamoylbenzoic acid, which derived originally from sulfonamides. Their diuretic effect is due to the inhibition of the Na-K-Cl-cotransport system in the distal part of Henle's loop. The compounds react with different affinity with the chloride binding site of the transporter. Bumetanide is among the most potent blockers with an IC50 of 0.2 microM. The compound was developed by P. W. FEIT, 1971; the saluretic response was described first by H. H. FREY 1972. Bumetanide has outgrown to become a tool for physiologists and pharmacologists in renal transport research. The compound has essentially contributed to the elucidation of the mechanisms of volume regulation of cells. Bumetanide is taken up into tubule cells and hepatocytes by active transport. The uptake in tubule cells ist mediated by an organic anion transporter, which is involved in the renal secretion of drugs. In the liver bumetanide is transporter by the bile acid carrier. The carrier is a multispecific drug transporter, too. It is not yet known, whether both drug transport systems contain identical membrane proteins. For this purpose bumetanide is currently used to investigate by photoaffinity labeling and functional expression cloning molecular principles of the drug elimination in kidney and liver.