Dan T, Tanaka H, Koga H
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical, Shizuoka, Japan.
J Pharmacol Exp Ther. 1990 May;253(2):437-43.
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-carb oxylic 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.
对六个品系的小鼠进行了研究，以寻找适合研究促尿酸排泄剂作用机制的动物模型。分别采用清除率法和吡嗪酰胺抑制试验来研究肾脏中尿酸排泄的机制和促尿酸排泄剂的作用方式。观察到尿尿酸排泄与内源性血浆尿酸水平呈负相关，提示不同品系之间尿酸的净重吸收可能存在差异。DBA/2N小鼠的尿酸排泄分数最低（0.278），促尿酸排泄剂对DBA/2N小鼠的作用与人相似。我们对DBA/2N小鼠尿酸排泄机制的广泛研究证明，该品系小鼠是研究促尿酸排泄剂的有用模型。AA-193（5-氯-7,8-二氢-3-苯基呋喃并[2,3-g]-1,2-苯并异恶唑-7-羧酸）是我们实验室开发的一种新型强效促尿酸排泄剂。在本研究中，对DBA/2N小鼠进行了AA-193测试，发现其作用方式与已知的促尿酸排泄剂不同。它似乎抑制近端小管的分泌前重吸收。
