The mode of action of bumetanide: inhibition of chloride transport across the amphibian cornea.

The diuretic drug bumetanide (10(-7 M) reduced the transmural potential difference and short-circuit current across the amphibian cornea in vitro. This effect reflected a decline in the outflux (endothelial to epithelial, or tear, side) of CI, which is the direction of its active transport. There was no change in the influx. The effect was slowly reversible at 10(-4) M and was about two times as great when the drug was on the endothelial as compared to the epithelial side. Furosemide had a similar effect on CI transport, but the dose-response curves of the two drugs were not parallel. Furosemide was about 60 to 200 times less potent than bumetanide. The effect of furosemide was about five times as great when the drug was on the endothelial rather than when it was placed on the epithelial side. Thiocyanate (2 x 10(-2) M) also inhibited the active CI transport across the cornea, but it was equally effective on either side of the membrane. Bumetanide had no effect on the passive CI movements across the toad lens or frog skin in vitro. The response of the skin differs from that of furosemide and thiocyanate. These observations of the effects of bumetanide on CI transport may be relevant to the mechanism of its diuretic actions in the kidney tubule.