Lansoprazole is an uncompetitive inhibitor of tissue-nonspecific alkaline phosphatase.
Lansoprazole, a known H(+)/K(+)-ATPase inhibitor, is currently used as a therapeutical option for the initial treatment of gastroesophageal reflux disease. Recently, lansoprazole has been found to be an inhibitor of cytosolic PHOSPHO1 (a phosphatase which hydrolyses phosphocholine and phosphoethanolamine), providing a possible therapeutical target to cure pathological mineralization. Since PHOSPHO1 is present inside matrix vesicles, we tested the effect of lansoprazole on matrix vesicles containing several key enzymes for the mineralization process including tissue-nonspecific alkaline phosphatase. We found that lansoprazole can inhibit in an uncompetitive manner tissue-nonspecific alkaline phosphatase. A K(i) value of 1.74 +/- 0.12 mM has been determined for the inhibition of tissue-nonspecific alkaline phosphatase by lansoprazole. Lansoprazole, currently used for treating gastroesophageal disease, by inhibiting PHOSPHO1 and tissue-nonspecific alkaline phosphatase could prevent hydroxyapatite-deposition disease and could serve as an adjunct treatment for osteoarthritis.
Delomenède
Mélanie
M
Universitné de Lyon, INSA de Lyon, CPE Lyon, CNRS UMR 5246 ICBMS, Villeurbanne Cedex, France.
Buchet
René
R
Mebarek
Saïda
S
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D002642:Chick Embryo; D022162:Cytoplasmic Vesicles / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D064747:Lansoprazole
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004791:Enzyme Inhibitors; D064747:Lansoprazole; D000469:Alkaline Phosphatase