A novel human hepatic organic anion transporting polypeptide (OATP2) - Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters
A novel human hepatic organic anion transporting polypeptide (OATP2) - Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters
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DOI：
10.1074/jbc.274.52.37161
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发表时间：
1999-12-24
影响因子：
4.8
通讯作者：
Kirchgessner, TG
中科院分区：
文献类型：
--
作者：
Hsiang, BN;Zhu, YJ;Kirchgessner, TG
一种新的人类有机转运蛋白OATP 2已被鉴定为转运牛磺胆酸、肾上腺雄激素硫酸脱氢表雄酮和甲状腺激素以及羟甲基戊二酰辅酶A还原酶抑制剂普伐他汀。OATP 2仅在肝脏中表达，与在肝脏和非肝脏组织中发现的所有其他已知转运蛋白亚型相反。OATP 2与其他家族成员有很大的差异，与其他四种亚型只有42%的序列同一性。此外，与其他亚型不同，OATP 2不转运地高辛或醛固酮。大鼠同种型oatp 1也显示转运普伐他汀，而OATP家族的其他成员，即大鼠oatp 2、人OATP和前列腺素转运蛋白，则不转运普伐他汀。顺式抑制研究表明，OATP 2和roatp 1也转运其他他汀类药物，包括洛伐他汀、辛伐他汀和阿托伐他汀。总之，OATP 2是一种新的有机阴离子转运蛋白，其与其他亚型中的每一种具有重叠但不相同的底物特异性，并且其肝脏特异性表达代表功能上不同的OATP同种型。oatp 1和oatp 2作为普伐他汀转运蛋白的鉴定表明，它们负责这种肝脏特异性羟甲基戊二酰-大鼠和人中的CoA还原酶抑制剂。
A novel human organic transporter, OATP2, has been identified that transports taurocholic acid, the adrenal androgen dehydroepiandrosterone sulfate, and thyroid hormone, as well as the hydroxymethylglutaryl-CoA reductase inhibitor, pravastatin. OATP2 is expressed exclusively in liver in contrast to all other known transporter subtypes that are found in both hepatic and nonhepatic tissues. OATP2 is considerably diverged from other family members, sharing only 42% sequence identity with the four other subtypes. Furthermore, unlike other subtypes, OATP2 did not transport digoxin or aldosterone. The rat isoform oatp1 was also shown to transport pravastatin, whereas other members of the OATP family, i.e. rat oatp2, human OATP, and the prostaglandin transporter, did not. Cis-inhibition studies indicate that both OATP2 and roatp1 also transport other statins including lovastatin, simvastatin, and atorvastatin. In summary, OATP2 is a novel organic anion transport protein that has overlapping but not identical substrate specificities with each of the other subtypes and, with its liver-specific expression, represents a functionally distinct OATP isoform, Furthermore, the identification of oatp1 and OATP2 as pravastatin transporters suggests that they are responsible for the hepatic uptake of this liver-specific hydroxymethylglutaryl-CoA reductase inhibitor in rat and man.