Inhibition of alkaline phosphatase by several diuretics.

Acetazolamide, furosemide, ethacrynic acid and chlorothiazide, diuretics of considerable structural diversity, inhibit alkaline phosphatase. The inhibition is reversible and the mechanism is of the mixed type, having both competitive and non-competitive characteristics. Ki is calculated to be 8.4, 7.0, 2.8 and 0.1 mmol/l for acetazolamide, furosemide, ethacrynic acid and chlorothiazide, respectively. Chlorothiazide is a much more potent inhibitor of alkaline phosphatase than the other three diuretics. The combination of ethacrynic acid and cysteine, itself an alkaline phosphatase inhibitor, is less inhibitory than ethacrynic acid alone. Rat and human kidney alkaline phosphatase are equally sensitive to chlorothiazide, ethacrynic acid and furosemide.