Effect of anti-inflammatory bowel disease drug, E3040, on urate transport in rat renal brush border membrane vesicles

To confirm the assumption that 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-py ridylmethyl)benzothiazole (E3040) acts on urate reabsorption by inhibiting urate-anion exchange at the luminal membrane of renal tubules, we investiga ted the inhibitory effect of E3040 and its two conjugated metabolites on hy droxyl ion (OH-) gradient-dependent urate uptake into brush border membrane vesicles from rat renal cortex and compared it with other uricosuric agent s. The order of potency was AA193 (5-chloro-7,8-dihydro-3-phenylfuro[2,3-g] -1,2-benzisoxazole-7-carboxylic acid)> benzbromarone > E3040 > probenecid > E3040 sulfate > E3040 glucuronide. Furthermore, kinetic analysis revealed that E3040 may be a competitive inhibitor of the OH- gradient-dependent upt ake of urate into brush border membrane vesicles. (C) 2000 Elsevier Science B.V. All rights reserved.