Biliary secretion of alpha-tocopherol and the role of the mdr2 P-glycoprotein in rats and mice.
Biliary secretion of alpha-tocopherol and the role of the mdr2 P-glycoprotein in rats and mice.
复制标题
α-生育酚的胆汁分泌和 mdr2 P-糖蛋白在大鼠和小鼠中的作用。
DOI：
10.1006/abbi.1997.0529
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发表时间：
1998
影响因子：
3.9
通讯作者：
Reed,DJ
中科院分区：
文献类型：
--
作者：
Mustacich,DJ;Shields,J;Horton,RA;Brown,MK;Reed,DJ
α-生育酚 (α-T) 分泌到胆汁中的机制尚不清楚；然而，我们之前已经证明，用胡椒基丁醚（PIP，1 g/kg）治疗会导致大鼠腹腔注射后 3 小时内胆汁中 α-T 和磷脂酰胆碱的输出增加，并且破坏微管的化学物质会阻止这两种物质的胆汁输出（Toxicol. Appl. Pharmacol.139, 411–417 (1996)）。 mdr2 基因编码的 P-糖蛋白 (Pgp) 已被证明可以将磷脂酰胆碱转运到胆汁中；因此，在本研究中，我们利用Pgp抑制剂维拉帕米来研究Pgp可能参与胆汁分泌α-T。当大鼠在 PIP 治疗前 10 分钟静脉注射维拉帕米（4 mg/kg）时，维拉帕米阻止了 PIP 诱导的胆汁 α-T 和磷脂酰胆碱输出的增加，并导致胆汁 α-T 输出显着低于对照组。此外，我们还确定 mdr2 敲除小鼠的胆汁 α-T 水平是野生型小鼠的 25%；此外，mdr2肝脏、肺脏和肾脏的α-T和谷胱甘肽水平与野生型不同。为了研究胆汁α-T的命运，我们将14C标记的α-T注射到大鼠的胆管插管中，并确定大约60%的放射性在1小时内被重新吸收。我们的结果表明，α-T 经历肠肝循环，并且 α-T 的胆汁分泌，基础上和化学处理后，取决于大鼠和小鼠中功能性 mdr2 Pgp 的存在。
The mechanism by which α-tocopherol (α-T) is secreted into the bile is not known; however, we have previously demonstrated that treatment with piperonyl butoxide (PIP, 1 g/kg) results in increased biliary output of both α-T and phosphatidylcholine within 3 h of ip injection in rats and that the biliary output of both substances was prevented by chemicals that disrupt microtubules (Toxicol. Appl. Pharmacol.139, 411–417 (1996)). The P-glycoprotein (Pgp) encoded by the mdr2 gene has been shown to transport phosphatidylcholine into the bile; therefore, in the current study, we utilized the Pgp inhibitor verapamil to investigate the possible involvement of Pgps in the biliary secretion of α-T. When rats were iv injected with verapamil (4 mg/kg) 10 min prior to PIP treatment, verapamil prevented the PIP-induced increases in biliary α-T and phosphatidylcholine output and resulted in biliary α-T outputs that were significantly less than controls. Also, we determined that the biliary α-T levels in mdr2 knockout mice were 25% of those in wildtype mice; furthermore, mdr2 liver, lung, and kidney levels of α-T and glutathione differed from those of wildtype. To investigate the fate of biliary α-T, we injected14C-labeled α-T into the bile duct cannulae of rats and determined that approximately 60% of the radioactivity was reabsorbed within 1 h. Our results indicate that α-T undergoes enterohepatic circulation and that the biliary secretion of α-T, basally and following chemical treatment, is dependent on the presence of a functioning mdr2 Pgp in rats and mice.
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影响因子：
6.5
作者：
F. Mattson;S. Grundy
通讯作者：
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影响因子：
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作者：
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影响因子：
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影响因子：
5.3
作者：
Wahl,PW;Warnick,GR;Albers,JJ;Hoover,JJ;Walden,CE;Bergelin,RO;Ogilvie,JT;Hazzard,WR;Knopp,RH
通讯作者：
Knopp,RH
影响因子：
6.5
作者：
W. S. Harris
通讯作者：
W. S. Harris