Role of the plasma membrane transporter of organic cations OCT1 and its genetic variants in modern liver pharmacology.
Role of the plasma membrane transporter of organic cations OCT1 and its genetic variants in modern liver pharmacology.
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DOI：
10.1155/2013/692071
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发表时间：
2013
影响因子：
--
通讯作者：
Marin JJ
中科院分区：
文献类型：
--
作者：
Lozano E;Herraez E;Briz O;Robledo VS;Hernandez-Iglesias J;Gonzalez-Hernandez A;Marin JJ
靶细胞对许多药物摄取的变化可能会极大地影响药理反应。因此，编码有机阳离子转运蛋白1(OCT1)的SLC22A1的下调可能会分别影响健康肝细胞和肝癌细胞对阳离子药物如二甲双胍和索拉非尼的反应。此外，遗传变异在致病过程中的预先存在或出现，可能会在相当程度上改变整体情况。一些罕见的OCT1变体增强了转运活性，而其他更常见的变体则损害了蛋白质成熟、质膜靶向或该载体的功能，从而降低了细胞内活性药物的浓度。在这里，我们回顾了OCT1在现代肝脏药理学中的作用的最新知识，包括使用阳离子药物治疗几种疾病，其中一些具有重要的临床意义，如糖尿病和原发性肝癌(胆管细胞癌和肝细胞癌)。我们的结论是，现代药理学必须考虑OCT1在健康肝脏和靶组织中的表达/功能的个体评估，特别是如果这是一种肿瘤，以便预测对阳离子药物的反应不足，并能够设计出具有最高成功机会的个性化药物治疗。
Changes in the uptake of many drugs by the target cells may dramatically affect the pharmacological response. Thus, downregulation of SLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively. Moreover, the overall picture may be modified to a considerable extent by the preexistence or the appearance during the pathogenic process of genetic variants. Some rare OCT1 variants enhance transport activity, whereas other more frequent variants impair protein maturation, plasma membrane targeting or the function of this carrier, hence reducing intracellular active drug concentrations. Here, we review current knowledge of the role of OCT1 in modern liver pharmacology, which includes the use of cationic drugs to treat several diseases, some of them of great clinical relevance such as diabetes and primary liver cancer (cholangiocarcinoma and hepatocellular carcinoma). We conclude that modern pharmacology must consider the individual evaluation of OCT1 expression/function in the healthy liver and in the target tissue, particularly if this is a tumor, in order to predict the lack of response to cationic drugs and to be able to design individualized pharmacological treatments with the highest chances of success.
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影响因子：
7.3
作者：
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通讯作者：
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影响因子：
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DOI：
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影响因子：
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通讯作者：
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