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-pyridylmethyl)benzothiazole (E3040) acts on urate reabsorption by inhibiting urate-anion exchange at the luminal membrane of renal tubules, we investigated the inhibitory effect of E3040 and its two conjugated metabolites on hydroxyl ion (OH(-)) gradient-dependent urate uptake into brush border membrane vesicles from rat renal cortex and compared it with other uricosuric agents. 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 uptake of urate into brush border membrane vesicles.
Yamada
H
H
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. hami-tky@umin.ac.jp
Kotaki
H
H
Itoh
T
T
Sawada
Y
Y
Iga
T
T
D000818:Animals; D052160:Benzothiazoles; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006878:Hydroxides / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology*; D014527:Uric Acid / Q000493:pharmacokinetics*; D014528:Uricosuric Agents / Q000494:pharmacology
D052160:Benzothiazoles; D005765:Gastrointestinal Agents; D006878:Hydroxides; D011725:Pyridines; D013844:Thiazoles; D014528:Uricosuric Agents; C095803:E 3040; D014527:Uric Acid; C031356:hydroxide ion