Effects of "loop" diuretics on ion transport by dog tracheal epithelium.
The "loop" diuretics MK-196, bumetanide, piretanide, and furosemide are all potent inhibitors of Cl transport by the dog's tracheal epithelium. In short-circuited tissues, the drugs caused significant decreases in both unidirectional Cl fluxes and in the net flux of Cl toward the lumen; the change in net Cl flux was not significantly different from the change in short-circuit current. The drugs had no effect on active Na absorption. All drugs caused a significant fall in tissue conductance. All drugs, except MK-196, were more potent from the serosal bath; MK-196 was equipotent from either side of the tissue. In experiments with isolated cells, the diuretics caused no significant changes in intracellular Na and K concentrations, a fall in intracellular Cl concentration, and approximately equal falls in Na and Cl influxes. These results suggest that the site of action of these drugs is on a basolateral linked Na-Cl entry process. Additional evidence for such a linked entry process was provided by experiments in which removal of Cl reduced Na influx and removal of Na reduced Cl influx.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005665:Furosemide / Q000494:pharmacology; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology; D007700:Kinetics; D009130:Muscle, Smooth / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D014132:Trachea / Q000502:physiology*
D002712:Chlorides; D004232:Diuretics; D007189:Indans; D013449:Sulfonamides; D002034:Bumetanide; D005665:Furosemide; D012964:Sodium; C013352:indacrinone; C015451:piretanide