Studies on the renal receptors of loop diuretics.

Abstract

The principal renal action of loop diuretics is to inhibit active NaCl transport in the thick ascending limb of the loop of Henle. However, apart from their specific tubular action, kidney function may be affected in other ways. By employing the enantiomeres of the new loop diuretic ozolinone, non-stereospecific increase in renal blood flow and inhibition of tubular secretion of p-aminohippurate and urate were found. In contrast, electrolyte transport in the loop of Henle was inhibited stereospecifically. Perfusion of single loops of rat kidneys in vivo with sugar-specific lectins suggested that a fucose-containing glycoprotein is involved in electrolyte transport in this tubular segment. Loop diuretics might interact with this glycoprotein, leading to inhibition of electrolyte transport. Evidence is presented to suggest that this protein is the Tamm-Horsfall protein. This fucose-containing glycoprotein is localized in the cell membranes of the thick ascending limb of the loop of Henle. It binds furosemide at concentrations very close to those required for inhibition of electrolyte transport in vivo. Furthermore, there is complete agreement between the sodium concentration necessary for stimulation of active transport in isolated thick ascending limbs of the loop of Henle and that necessary for binding of furosemide to the Tamm-Horsfall glycoprotein.