Decreased activity and expression of intestinal oligopeptide transporter PEPT1 in rats with hyperthyroidism in vivo
Decreased activity and expression of intestinal oligopeptide transporter PEPT1 in rats with hyperthyroidism in vivo
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DOI：
10.1023/b:pham.0000029285.45101.ee
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发表时间：
2004-06-01
影响因子：
3.7
通讯作者：
Inui, K
中科院分区：
文献类型：
--
作者：
Ashida, K;Katsura, T;Inui, K
目的。为了研究体内甲状腺激素状态对PEPT1的影响，我们检测了甲状腺功能正常和甲状腺功能亢进大鼠小肠中PEPT1的活性和表达。用L-甲状腺素（12 mg/L）灌胃21 d诱导大鼠甲状腺功能亢进。采用小肠膨化制剂和原位肠袢技术测定转运活性。采用竞争性聚合酶链反应和Western blotting分别检测PEPT1 mRNA和蛋白的表达。在甲状腺功能亢进的大鼠中，膨化小肠制剂对[C-14]甘氨酸肌氨酸的摄取明显减少，而甲基- α - d -[C-14(U)]-葡萄糖吡喃苷的摄取没有改变。动力学分析表明，甲亢大鼠对[C-14]甘氨酸肌氨酸摄取的V-max值显著降低，而Km值不受影响。甲亢大鼠空肠内注射[C-14]甘氨酸肌氨酸后门静脉平均浓度也降低。此外，甲状腺功能亢进导致小肠PEPT1 mRNA的表达显著降低，而Na+/葡萄糖共转运体（SGLT1） mRNA的表达未发生变化。甲状腺功能亢进大鼠小肠中PEPT1蛋白水平也明显降低。这些结果表明，甲状腺功能亢进大鼠小肠中PEPT1的活性和表达降低。
Purpose. To examine the effect of thyroid hormone status on PEPT1 in vivo, the activity and expression of PEPT1 in the small intestine were examined in euthyroid and hyperthyroid rats.Methods. Hyperthyroidism was induced by treating rats with L-thyroxine (12 mg/L) in the drinking water for 21 days. Transport activity was measured by everted small intestinal preparations and in situ intestinal loop technique. Expressions of PEPT1 mRNA and protein were evaluated by competitive polymerase chain reaction and Western blotting, respectively.Results. The uptake of [C-14]glycylsarcosine by everted small intestinal preparations was significantly decreased in hyperthyroid rats, whereas that of methyl-alpha-D-[C-14(U)]-glucopyranoside was not altered. Kinetic analysis showed that the V-max value for [C-14] glycylsarcosine uptake was significantly decreased in hyperthyroid rats, whereas the Km value was not affected. The mean portal vein concentrations after intrajejunal administration of [C-14] glycylsarcosine were also decreased in hyperthyroid rats. Moreover, hyperthyroidism caused a significant decrease in the expression of PEPT1 mRNA in the small intestine, whereas the expression of Na+/glucose cotransporter (SGLT1) mRNA was not changed. The level of PEPT1 protein was also decreased in the small intestine of hyperthyroid rats.Conclusions. These results indicate that in hyperthyroid rats, the activity and expression of PEPT1 were decreased in the small intestine.