Bumetanide stimulation of sodium permeability of the apical membrane of toad urinary bladder

The effects of bumetanide on Na transport in the isolated toad urinary bladder were investigated. When applied to the serosal side, this loop diuretic inhibited Na transport. By contrast, when applied to the mucosal side, it stimulated Na transport by increasing the apical Na permeability. These dual effects of bumetanide were also observed with the loop diuretic furosemide. The mucosal action of bumetanide was attributable to release of Na self-inhibition, as evidenced by its dependency on mucosal Na concentration and its interaction with another apical Na permeability stimulator, p-chloromercuriphenyl sulfonate. The stimulatory action of bumetanide was not reduced by the natriferic effect of antidiuretic hormone, but it was totally blockable by the epithelial Na channel blocker amiloride. Bumetanide, however, caused a leftward shift of the concentration-response curve of amiloride on Na current as predicted from its effect on Na self-inhibition. This stimulatory activity of bumetanide and furosemide as demonstrated in the in vitro isolated amphibian epithelia suggests that these loop diuretics also have the potential to stimulate Na transport at the distal portion of the mammalian nephron. Thus, this property of these diuretics might be one of the factors contributing to the observation of increased Na reabsorption along the distal tubule after in vivo administration of furosemide and piretanide as reported in some micropuncture studies.