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C57BL/6J小鼠中的高牛磺酸尿症:肾基底外侧膜转运改变。

Hypertaurinuria in the C57BL/6J mouse: altered transport at the renal basolateral membrane.

作者信息

Rozen R, Scriver C R, Mohyuddin F

出版信息

Am J Physiol. 1983 Feb;244(2):F150-5. doi: 10.1152/ajprenal.1983.244.2.F150.

Abstract

The C57BL/6J mouse is an inbred strain with selective hypertaurinuria. C3H/HeJ mice (control) and C57BL/6J mice have comparable values for plasma taurine and renal creatinine clearance but significantly different fractional taurine excretion: C3H mice, 0.15 +/- 0.03; C57BL mice, 0.44 +/- 0.08 (P less than 0.01). C57BL mice fed control diet have significantly higher renal cortex taurine (11.5 +/- 0.4 mumol/g wet wt, mean +/- SE) relative to C3H mice (10.5 +/- 0.5 mumol/g, P less than 0.05); the difference is magnified when mice are fed low protein or low sulfur amino acid diet and experience renal adaptation with enhanced taurine transport at the luminal membrane (P less than 0.01). Taurine transport by purified brush border membrane vesicles is similar in the two strains fed control diet. On the other hand, renal cortex slices show the following differences: 1) net uptake of taurine at 0.11 mM is lower in C57BL slices at initial rates and at steady state; 2) the difference in uptake between strains is magnified in the presence of phlorizin, an inhibitor of taurine efflux; 3) efflux of taurine from preloaded slices is less per unit time in C57BL mice; and 4) uptake differences are specific for taurine. These findings are not accountable to differences in taurine oxidation, slice weight, or water spaces. They indicate that hypertaurinuria in the C57BL/6J strain is a function of decreased basolateral membrane permeability to taurine at physiologic concentrations.

摘要

C57BL/6J小鼠是一种具有选择性高牛磺酸尿症的近交系。C3H/HeJ小鼠(对照)和C57BL/6J小鼠的血浆牛磺酸和肾肌酐清除率值相当,但牛磺酸排泄分数显著不同:C3H小鼠为0.15±0.03;C57BL小鼠为0.44±0.08(P<0.01)。与C3H小鼠(10.5±0.5 μmol/g,P<0.05)相比,喂食对照饮食的C57BL小鼠肾皮质牛磺酸含量显著更高(11.5±0.4 μmol/g湿重,平均值±标准误);当小鼠喂食低蛋白或低硫氨基酸饮食并经历肾适应性变化,管腔膜牛磺酸转运增强时,差异会放大(P<0.01)。在喂食对照饮食的两个品系中,纯化的刷状缘膜囊泡对牛磺酸的转运相似。另一方面,肾皮质切片显示出以下差异:1)在初始速率和稳态下,C57BL切片中0.11 mM牛磺酸的净摄取量较低;2)在根皮苷(一种牛磺酸外排抑制剂)存在的情况下,品系间的摄取差异会放大;3)C57BL小鼠中,预先加载的切片单位时间内牛磺酸的外排量较少;4)摄取差异对牛磺酸具有特异性。这些发现不能归因于牛磺酸氧化、切片重量或水间隙的差异。它们表明,C57BL/6J品系中的高牛磺酸尿症是生理浓度下基底外侧膜对牛磺酸通透性降低的结果。

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