Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis
Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis
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DOI：
10.3748/wjg.v18.i44.6387
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发表时间：
2012-11-28
影响因子：
4.3
通讯作者：
Monica Torres, Adriana
中科院分区：
文献类型：
--
作者：
Brandoni, Anabel;Herminia Hazelhoff, Maria;Monica Torres, Adriana
阻塞性黄疸发生在患有胆石症和影响胰腺和胆总管的肿瘤的患者中。在这种病理过程中，药物的吸收、分布和消除受到损害。长期胆汁淤积可能会改变肝肾功能。内酰胺抗生素、利尿剂、非甾体抗炎药、几种抗病毒药物以及内源性化合物被归类为有机阴离子。肝和肾有机阴离子转运途径在这些化合物的药代动力学中起着关键作用。已经证明，急性肝外胆汁淤积与肾脏消除有机阴离子的增加有关。目前的工作描述了肝外胆汁淤积中肾和肝有机阴离子转运蛋白的表达和功能调节的分子机制，例如多药耐药相关蛋白2、有机阴离子转运多肽1、有机阴离子转运蛋白3、胆转运酶、溴磺酞/胆红素结合蛋白、有机阴离子转运蛋白1和钠依赖性胆汁盐转运蛋白。肾脏有机阴离子转运蛋白表达的调节构成了克服有机阴离子消除肝功能障碍的代偿机制。 (C)2012年百事登。版权所有。
Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct. The absorption, distribution and elimination of drugs are impaired during this pathology. Prolonged cholestasis may alter both liver and kidney function. Lactam antibiotics, diuretics, non-steroidal anti-inflammatory drugs, several antiviral drugs as well as endogenous compounds are classified as organic anions. The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds. It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions. The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis, such as multidrug resistance-associated protein 2, organic anion transporting polypeptide 1, organic anion transporter 3, bilitranslocase, bromosulfophthalein/bilirubin binding protein, organic anion transporter 1 and sodium dependent bile salt transporter. The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions. (C) 2012 Baishideng. All rights reserved.