Greven J
Clin Exp Hypertens A. 1983;5(2):193-208. doi: 10.3109/10641968309048821.
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.
袢利尿剂的主要肾脏作用是抑制髓袢升支粗段的主动氯化钠转运。然而，除了其特定的肾小管作用外，肾脏功能可能还会受到其他方面的影响。通过使用新型袢利尿剂奥唑啉酮的对映体，发现肾血流量有非立体特异性增加，对氨基马尿酸和尿酸的肾小管分泌受到抑制。相比之下，髓袢中电解质转运受到立体特异性抑制。用糖特异性凝集素对大鼠肾脏的单个髓袢进行体内灌注表明，一种含岩藻糖的糖蛋白参与了该肾小管段的电解质转运。袢利尿剂可能与这种糖蛋白相互作用，从而导致电解质转运受到抑制。有证据表明这种蛋白质是Tamm-Horsfall蛋白。这种含岩藻糖的糖蛋白定位于髓袢升支粗段的细胞膜上。它在非常接近体内抑制电解质转运所需的浓度下结合速尿。此外，在髓袢升支粗段分离标本中刺激主动转运所需的钠浓度与速尿与Tamm-Horsfall糖蛋白结合所需的钠浓度完全一致。
