Article ID Journal Published Year Pages File Type
9921247 European Journal of Pharmacology 2005 9 Pages PDF
Abstract
JTP-59557 [(−)-4-(2-tert-Butyl-4,5-dichlorophenyl)-5-(5-trifluoromethylpyridin-2-ylsulfanyl)-4H-[1,2,4]triazol-3-ol] showed an inhibitory effect on Na+-dependent inorganic phosphate (Pi) transport in intestinal brush border membrane vesicles with an IC50 value of 0.40 μM in rabbit and with an IC50 of 0.19 μM in rat, without affecting Na+-independent Pi and Na+-dependent d-glucose transport activities. In Chinese hamster ovary (CHO) cells expressing human type IIb Na/Pi cotransporter (type IIb), JTP-59557 decreased human type IIb-mediated Pi uptake with an IC50 of 0.12 μM. In rabbit intestinal brush border membrane vesicles, JTP-59557 behaved as a noncompetitive inhibitor with respect to Pi. In an in vivo study, single administration of JTP-59557 significantly decreased the intestinal Pi absorption rate, when either Pi solution or laboratory chow was given to rats. In this report, we show that JTP-59557 is a potent, selective, stereospecific, noncompetitive inhibitor of intestinal Na/Pi cotransporters including type IIb, and it may represent a new class of intestinal Pi absorption inhibitor.
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