Modulation of P-glycoprotein expression in hyperthyroid rat tissues
Modulation of P-glycoprotein expression in hyperthyroid rat tissues
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DOI：
10.1124/dmd.105.004770
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发表时间：
2005-11-01
影响因子：
3.9
通讯作者：
Inui, KI
中科院分区：
文献类型：
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作者：
Nishio, N;Katsura, T;Inui, KI
p -糖蛋白（Pgp）在各种正常组织中表达，在药物吸收和处置中起重要作用。此外，Pgp表达水平的改变被认为与许多药物的药代动力学的个体间和个体内变异性有关。由于各种药物的药代动力学特性在甲状腺疾病患者中发生改变，我们检测了Pgp和mdr1a/1b mRNA在甲状腺功能正常和甲状腺功能高的大鼠肾脏、肝脏、空肠和回肠中的表达。Western blot分析显示，Pgp在甲状腺功能亢进大鼠的肾脏和肝脏中表达明显升高。相比之下，空肠和回肠则略有增加。甲状腺功能亢进大鼠肾脏中mdr1a/1b mRNA水平显著升高。甲状腺功能亢进大鼠肝脏、空肠和回肠中均无升高。在甲状腺功能亢进大鼠肝脏中，胆盐输出泵和mdr2 mRNA的表达水平也没有变化。综上所述，这些发现表明甲状腺激素以组织选择性的方式诱导Pgp的表达，并且mdr1a/1b mRNA在甲亢状态下的表达调节在不同组织中是不同的。
P-glycoprotein (Pgp) is expressed in various normal tissues and plays an important role in drug absorption and disposition. In addition, it is supposed that alterations in the expression levels of Pgp are involved in the inter- and intraindividual variability of pharmacokinetics of many drugs. Since pharmacokinetic properties of various drugs are altered in patients with thyroid disorders, we examined the expression of Pgp and mdr1a/1b mRNA in the kidney, liver, jejunum, and ileum from euthyroid and hyperthyroid rats. Western blot analysis revealed that Pgp expression was markedly increased in the kidney and liver of hyperthyroid rats. In contrast, it was slightly increased in the jejunum and ileum. mdr1a/1b mRNA levels were significantly increased in the kidney of hyperthyroid rats. However, they were not increased in the liver as well as in the jejunum and ileum of hyperthyroid rats. Expression levels of bile salt export pump and mdr2 mRNA were also unchanged in hyperthyroid rat liver. Taken together, these findings suggest that thyroid hormone induces Pgp expression in a tissue-selective manner, and that the modulation of mdr1a/1b mRNA expression in the hyperthyroid state varies among tissues.