Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid.

Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid.
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大鼠静脉注射黄尿酸可利尿,丙磺舒可抑制利尿。

DOI:
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发表时间:
2014
期刊:
Biomedical research
影响因子:
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通讯作者:
T. Nabekura
T. Nabekura
中科院分区:
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文献类型:
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作者:
Y. Uwai;Y. Nakashima;Emi Honjo;T. Kawasaki;T. Nabekura

文献摘要

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色氨酸代谢产物黄尿酸的硫酸盐和葡萄糖苷的结合物显示出尿钠排泄作用。黄尿酸的磺基转移酶在肾脏近端小管和肝脏中起作用,产生黄尿酸的硫酸盐,我们最近发现黄尿酸是肾脏有机阴离子转运蛋白OAT 1的底物。本研究的目的是研究OAT 1转运与黄尿酸相关的利尿作用之间的关系。药物转运实验表明丙磺舒抑制大鼠OAT 1(rOAT 1)对黄尿酸的摄取。虽然大鼠静脉注射大剂量黄尿酸没有发现利尿作用,但增加其输注表现出尿钠排泄。丙磺舒同时给药可显著减少尿量和尿钠排泄量。这些结果表明黄尿酸给药具有利尿作用,并且对丙磺舒敏感。rOAT 1介导的黄尿酸转运可能至少部分有助于其利尿作用。
The conjugates with sulfate and glucoside of xanthurenic acid, a tryptophan metabolite, were reported to show natriuresis. Sulfotransferase for xanthurenic acid works in the renal proximal tubule to produce the sulfate of xanthurenic acid as well as the liver, and we recently found that xanthurenic acid is a substrate of renal organic anion transporter OAT1. The purpose of this study was to examine relationship between the transport by OAT1 and diuresis related with xanthurenic acid. Drug transport experiment using Xenopus laevis oocytes represented that probenecid inhibited xanthurenic acid uptake by rat OAT1 (rOAT1). Although no diuresis was recognized by the intravenous injection of xanthurenic acid as a bolus in rats, the addition of its infusion exhibited natriuresis. Simultaneous administration of probenecid significantly decreased the urine volume and excreted amounts of sodium into urine. These findings showed the diuresis by the xanthurenic acid administration, and it was probenecid-sensitive. The rOAT1-mediated transport of xanthurenic acid might, at least in part, contribute to its diuretic effect.