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

机译:在大鼠中静脉内注射黄原酸的利尿作用和丙磺舒的抑制作用

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摘要

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.
机译:据报道,与一种色氨酸代谢产物黄嘌呤酸的硫酸盐和葡萄糖苷结合时,显示出利钠作用。黄原酸的磺基转移酶在肾小管中起作用,产生黄原酸的硫酸盐以及肝脏,并且我们最近发现黄原酸是肾有机阴离子转运蛋白OAT1的底物。这项研究的目的是检查OAT1的转运与与黄腐酸有关的利尿之间的关系。使用非洲爪蟾卵母细胞的药物转运实验表明,丙磺舒抑制了大鼠OAT1(rOAT1)对黄嘌呤酸的吸收。尽管通过静脉注射黄嘌呤酸作为大剂量推注大鼠未发现利尿剂,但其输注的添加表现出利尿作用。同时施用丙磺舒可显着减少尿液量,并向尿中排泄钠。这些发现表明黄原酸的施用有利尿,并且对丙磺舒敏感。 rOAT1介导的黄原酸的转运可能至少部分有助于其利尿作用。

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