Nishio Naoki, Katsura Toshiya, Ashida Kayoko, Okuda Masahiro, Inui Ken-Ichi
Department of Pharmacy, Kyoto University Hospital, Kyoto 606-8507, Japan.
Drug Metab Dispos. 2005 Nov;33(11):1584-7. doi: 10.1124/dmd.105.004770. Epub 2005 Aug 3.
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.
P-糖蛋白（Pgp）在多种正常组织中表达，在药物吸收和处置中起重要作用。此外，据推测Pgp表达水平的改变与许多药物药代动力学的个体间和个体内变异性有关。由于甲状腺疾病患者各种药物的药代动力学特性会发生改变，我们检测了甲状腺功能正常和甲状腺功能亢进大鼠的肾脏、肝脏、空肠和回肠中Pgp以及mdr1a/1b mRNA的表达。蛋白质免疫印迹分析显示，甲状腺功能亢进大鼠的肾脏和肝脏中Pgp表达明显增加。相比之下，空肠和回肠中的表达略有增加。甲状腺功能亢进大鼠肾脏中mdr1a/1b mRNA水平显著增加。然而，在甲状腺功能亢进大鼠的肝脏以及空肠和回肠中，它们并未增加。甲状腺功能亢进大鼠肝脏中胆盐输出泵和mdr2 mRNA的表达水平也未改变。综上所述，这些发现表明甲状腺激素以组织选择性方式诱导Pgp表达，并且甲状腺功能亢进状态下mdr1a/1b mRNA表达的调节在不同组织中有所不同。
