Effects of "loop" diuretics on ion transport by dog tracheal epithelium

Abstract

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.

Regulation of sodium absorption by canine tracheal epithelium.

“…Although many neurohumoral agents are known to regulate Cl-secretion, much less is known about the direct regulation of Na+ absorption. Previous reports show that many agents that stimulate Cl-secretion produce a simultaneous fall in the rate of Na+ absorption (2)(3)(4). However, such a decrease might be secondary to a decrease in the electrochemical gradient favoring Na+ entry into the cell across the apical membrane: secretagogues depolarize the electrical potential difference across the apical membrane (5) and increase intracellular Na+ activity (6).…”

Stimulation of Na Absorption by the Antiasthmatic Kampo Drug Saiboku-To in Cultured Airway Epithelium.

“…This notion is based on the findings that TJ-96 dose-dependently increased SCC, a bioelectric parameter that reflects net ion movement across the epithelium (15), and that this increase was abolished by pretreat ment of cells with amiloride that inhibits Na conductance at the apical membrane (10) but not by the Cl transport blocker diphenyl amine-2-carboxylate (11) or furosemide, an in hibitor of Cl transport (12). Simultaneous in creases in PD and G are compatible with our notion because these parameters reflect the electromotive force produced by ion transport and the membrane permeability for such elec trolytes, respectively (16).…”

“…To assess whether the TJ-96-induced changes in SCC were associated with Na ab sorption and/or Cl secretion by the epitheli um, cells were pretreated for 30 min with each of the following drugs: amiloride (10-4 M), a Na channel blocker (10); diphenylamine-2 carboxylate (10-4 M), a CI channel blocker (11); furosemide (104 M), a Cl transport in hibitor (12), and TJ-96 (1 mg/ml) was then added to the mucosal bath.…”

Mechanical Forces Impair Alveolar Ion Transport Processes – A Putative Mechanism Contributing to the Formation of Pulmonary Edema

“…A major advantage as well as a prerequisite of this technique is the use of an intact epithelial layer consisting of differentiated polar cells. Although this technique is applicable for many freshly dissected epithelia including airway epithelia from mammals (Olver et al, 1975;Widdicombe and Welsh, 1980), the use of mammalian alveolar epithelium for elaborating this technique is not possible. This is due to the complex anatomy reasoned by miniaturization of the gas-exchanging region.…”