Blockers of Active Transport in the Thick Ascending Limb of the Loop of Henle
Loop diuretics of the furosemide type are well known blockers of active NaCl reabsorption in the medullary and in the cortical thick ascending limb of the loop of Henle (1). They interact with one of the Cl- binding sites of the Na+2Cl-K+ carrier. Recently, we have developed a new class of substances which interferes with the Cl- channels in the baso lateral membrane of the same nephron segments and blocks the conductive transfer of Cl- from the cell to the peritubule side (2,3). The same type of substance blocks chloride channels in a variety of other epithelia: colon (unpublished from the authors’ laboratory), trachea (M. Welsh, personal communication), sweat duct (4), cortical collecting tubule (5), and rectal gland (6). Figure 1 indicates that both classes of substances, the loop diuretics of furosemide type and the chloride channel blockers, share some of their chemical structure, and that both compounds are similar to torasemide. Torasemide is a new diuretic interfering with the Na+2C1-K+ carrier and also. at about 100 times higher concentrations, with chloride channels (7).
KeywordsCarboxylate Phenyl Pyridine Luminal Peri
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