Mechanism of uricosuric action of AA-193 in DBA/2N mice

T. Dan, H. Tanaka, H. Koga

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Six strains of mice were investigated to find an animal model suitable for researching the mechanism of uricosuric agents. A clearance method and a pyrazinamide suppression test were used to examine the mechanism of urate excretion in the kidney and the mode of action of uricosurics, respectively. The negative correlation between the urinary urate excretion and the endogenous plasma urate level was observed, suggesting the net reabsorption of urate may vary between strains. DBA/2N mice showed the lowest fractional excretion of urate (0.278), and the effects of uricosurics on DBA/2N mice are analogous to those of humans. Our extensive study of the mechanism of urate excretion in DBA/2N mice has proven that the mouse strain is a useful model for the study of uricosurics. AA-193 (5-chloro-7,8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7- carboxylic acid) is a potent new uricosuric agent developed in our laboratory. In the present study, AA-193 was tested in DBA/2N mice and found to have a mode of action different from well-known uricosuric agents. It appeared to inhibit presecretory reabsorption in the proximal tubules.

Original languageEnglish
Pages (from-to)437-443
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume253
Issue number2
Publication statusPublished - 1990 Jan 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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