Evaluation of drug effects on rabbit intestinal alkaline phosphatase activity

ABSTRACT

Alkaline phosphatase [AP] plays an important role in the availability and absorption of inorganic phosphate [Pi] through the intestine. In this study we have investigated the effects of various orally administered drugs on AP prepared from rabbit intestinal mucosa. The enzyme had a Km of 0.5 X 10-3 M at pH 10.5 and produced linear reaction rates both with respect to enzyme and substrate concentration. The AP was totally inhibited by 2.68 mM EDTA. An analysis of the effects of various drugs on AP showed that cysteine, aminophylline, neomycin, theophylline, pilocarpine, caffeine, aspirin and threonine, in descending order of potency, inhibited intestinal AP in a concentration-dependent manner. Acetylcholine, carbachol, alropine, hyoscine, ampicillin, isoniazide, polymyxin B, sulphamethoxazole, trimethoprim, indomethacin, p-acetamidophenol, papaverine, cyclazine, diphenhydramine, hydrocortisone, tyramine, streptomycin, and promethazine had no effect on intestinal AP. Our data showed that a number of drugs inhibited AP. It is tempting to speculate that the inhibition produced by various drugs may involve interference with absorption processes of Pi or the availability of Pi in the gastrointestinal tract