Impaired ability to increase water excretion in mice lacking the taurine transporter gene TAUT
Impaired ability to increase water excretion in mice lacking the taurine transporter gene TAUT
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DOI：
10.1007/s00424-005-1499-y
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发表时间：
2006-02-01
影响因子：
4.5
通讯作者：
Vallon, V
中科院分区：
文献类型：
--
作者：
Huang, DY;Boini, KM;Vallon, V
细胞牛磺酸的摄取或释放抵消细胞体积的变化。 Na+ 偶联牛磺酸转运蛋白 TAUT 介导细胞对牛磺酸的集中摄取。低渗性抑制加压素分泌可能涉及视上核神经胶质细胞释放牛磺酸。我们比较了缺乏 TAUT 的小鼠 (taut(-/-)) 和野生型同窝小鼠 (taut(+/+)) 的肾功能。我们在 taut(-/-) 小鼠中观察到肾牛磺酸丢失和随后的低牛磺酸血症。在自由饮水的情况下，在 taut(-/-) 和 taut+/+ 小鼠中，血浆和尿液渗透压、尿流速以及尿液排泄以及 Na+ 和 K+ 血浆浓度相似，而 taut(-/-) 小鼠中尿素血浆浓度升高。口服水负荷（1 毫升/16 克体重）在两种基因型中都会诱导类似的利尿作用。然而，在尿流量正常化后立即重复口服水负荷，会导致拉紧（-/-）小鼠的利尿延迟和尿加压素/肌酐比值升高。相比之下，不同基因型对加压素 V-2 受体阻断的重复利尿反应没有差异。两种基因型缺水 36 小时都会导致类似的抗利尿作用和尿渗透压增加。剥夺水后自由饮水后，紧张（-/-）小鼠继续浓缩尿液长达6天，而紧张（+/+）小鼠迅速恢复到正常尿渗透压。在基础条件下，尿液加压素/肌酐比值和血浆醛固酮浓度没有差异，但在禁水后 6 天，紧张（-/-）小鼠显着高于紧张（+/+）小鼠。总之，紧张（-/-）小鼠患有肾牛磺酸损失，降低尿液渗透压和增加尿水排泄的能力受损。后一种缺陷可能存在于肾外，是由牛磺酸在抑制加压素释放中的作用引起的，这种作用在紧张（-/-）小鼠中可能会减弱。
Cellular taurine uptake or release counteracts alterations of cell volume. Na+-coupled taurine transporter TAUT mediates concentrative cellular uptake of taurine. Inhibition of vasopressin secretion by hypotonicity may involve taurine release from glial cells of supraoptic nucleus. We compared renal function of mice lacking TAUT (taut(-/-)) and wild-type littermates (taut(+/+)). We observed renal taurine loss and subsequent hypotaurinemia in taut(-/-) mice. With free access to water, plasma and urine osmolality, urinary flow rate as well as urinary excretion and plasma concentrations of Na+ and K+ were similar in taut(-/-) and taut+/+ mice, whereas plasma concentrations of urea were enhanced in taut(-/-) mice. An oral water load ( 1 ml/16 g body weight) induced a similar diuresis in both genotypes. Repeating the oral water load immediately after normalization of urine flow rate, however, resulted in delayed diuresis and higher urinary vasopressin/ creatinine ratios in taut(-/-) mice. In comparison, the repeated diuretic response to vasopressin V-2 receptor blockade was not different between genotypes. Water deprivation for 36 h led to similar antidiuresis and increases of urinary osmolality in both genotypes. Upon free access to water after deprivation, taut(-/-) mice continued to concentrate urine up to 6 days, while taut(+/+) mice rapidly returned to normal urinary osmolality. Urinary vasopressin/ creatinine ratios and plasma aldosterone concentrations were not different under basal conditions but were significantly higher in taut(-/-) mice than in taut(+/+) mice at 6 days after water deprivation. In conclusion, taut(-/-) mice suffer from renal taurine loss and impaired ability to lower urine osmolality and to increase urinary water excretion. The latter defect could reside extrarenally and result from a role of taurine in the suppression of vasopressin release which may be attenuated in taut(-/-) mice.