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NAP-牛磺酸的肾脏转运

Renal transport of NAP-taurine.

作者信息

Stokols M F, Koschier F J, Goldinger J M, Hong S K

出版信息

Am J Physiol. 1981 Jul;241(1):F9-13. doi: 10.1152/ajprenal.1981.241.1.F9.

Abstract

The renal transport of N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate (NAP-taurine), a potential photoaffinity label, was studied using the rabbit renal cortical slice and the isolated perfused rat kidney. NAP-taurine inhibited the slice accumulation of PAH in a dose-dependent manner (ID50 = 2.5 X 10(-5) M). It accumulated to a steady-state slice-to-medium concentration ratio of 14. However, NAP-taurine was not toxic to the tissue, as it did not influence the accumulation of the organic cation tetraethylammonium. NAP-taurine transport was saturable and its accumulation was inhibited by the metabolic inhibitors PAH, probenecid, 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS), ouabain, and the absence of sodium. Kinetic studies showed that the Km for NAP-taurine is 3.5 X 10(-5) M, and also that PAH competitively inhibits NAP-taurine influx with a Ki of 1.2 X 10(-3) M. Experiments with the rat isolated perfused kidney gave the NAP-taurine-to-inulin clearance ratio of approximately 5, indicating net tubular secretion. DIDS significantly reduced this clearance ratio to 0.8. The results suggest NAP-taurine is handled by the kidney in a manner analogous to PAH and may thus be useful as a photoaffinity label for the renal organic anion transport system.

摘要

利用兔肾皮质切片和离体灌注大鼠肾脏,对一种潜在的光亲和标记物N-(4-叠氮基-2-硝基苯基)-2-氨基乙磺酸盐(NAP-牛磺酸)的肾脏转运进行了研究。NAP-牛磺酸以剂量依赖方式抑制PAH在切片中的蓄积(半数抑制浓度=2.5×10⁻⁵M)。它蓄积至切片与介质浓度的稳态比为14。然而,NAP-牛磺酸对组织无毒,因为它不影响有机阳离子四乙铵的蓄积。NAP-牛磺酸的转运是可饱和的,其蓄积受到代谢抑制剂PAH、丙磺舒、4,4'-二异硫氰酸-2,2'-二磺酸芪(DIDS)、哇巴因以及无钠环境的抑制。动力学研究表明,NAP-牛磺酸的米氏常数为3.5×10⁻⁵M,并且PAH以1.2×10⁻³M的抑制常数竞争性抑制NAP-牛磺酸的流入。对大鼠离体灌注肾脏的实验得出NAP-牛磺酸与菊粉的清除率比值约为5,表明有净肾小管分泌。DIDS显著将该清除率比值降至0.8。结果表明,NAP-牛磺酸在肾脏中的处理方式类似于PAH,因此可能作为肾脏有机阴离子转运系统的光亲和标记物有用。

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