Interaction of six protoberberine alkaloids with human organic cation transporters 1, 2 and 3
Interaction of six protoberberine alkaloids with human organic cation transporters 1, 2 and 3
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六种原小檗碱生物碱与人体有机阳离子转运蛋白 1、2 和 3 的相互作用
DOI：
10.3109/00498254.2015.1056283
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发表时间：
2016-02
期刊：
影响因子：
1.8
通讯作者：
Huidi Jiang
中科院分区：
文献类型：
--
作者：
Liping Li;Siyuan Sun;Yayun Weng;Feifeng Song;Sisi Zhou;Mengru Bai;Hui Zhou;Su Zeng;Huidi Jiang
1.有机阳离子转运蛋白（OCTs）对药物的安全性和有效性起着重要作用。 原小檗碱类生物碱是一种普遍存在的有机阳离子或弱碱，具有显著的生物活性。本研究以稳定表达人OCT 1、OCT 2和OCT 3.2的MDCK细胞为研究对象，探讨黄连碱、药根碱、表小檗碱、小檗红碱、巴马汀和可达琳等生物碱与OCT的相互作用。结果表明，黄连碱、药根碱、表小檗碱、小檗红碱、巴马汀和可达琳等生物碱均能显著抑制MDCK-hOCT细胞对MPP+的摄取，IC 50为0.931-9.65 μ M。 黄连碱、药根碱和表小檗碱是所有hOCT的底物，Km值为0.273 - 5.80 μ M，而小檗红碱是hOCT 1和hOCT 2的底物，而不是hOCT 3的底物，Km值分别为1.27和1.66 μ M。在表达hOCT 1-P341 L或hOCT 2-A270 S变体的MDCK细胞中黄连碱的转运能力显著高于野生型（WT）细胞，克林特（Vmax/Km）分别为379 ± 7.4和433 ± 5.7 μ l/mg蛋白/min。 表小檗碱和小檗红碱是hOCT 1、hOCT 2和/或hOCT 3的高亲和力底物。此外，变体（0CT1-P341L和0CT2-A270S）具有比WT hOCT更高的对黄连碱的转运能力。
1. Organic cation transporters (OCTs) play an important role in drug safety and efficacy. Protoberberine alkaloids are ubiquitous organic cations or weak bases with remarkable biological actives. This study was to elucidate the potential interaction of alkaloids (coptisine, jatrorrhizine, epiberberine, berberrubine, palmatine and corydaline) with OCTs using Madin–Darby canine kidney (MDCK) cells stably expressing human OCT1, OCT2 and OCT3.2. All the tested alkaloids significantly inhibited the uptake of MPP+, a model OCT substrate, in MDCK-hOCTs cells with the IC50of 0.931–9.65 μM. Additionally, coptisine, jatrorrhizine and epiberberine were substrates of all the hOCTs with theKmof 0.273–5.80 μM, whereas berberrubine was a substrate for hOCT1 and hOCT2, but not for hOCT3, theKmvalues were 1.27 and 1.66 μM, respectively. The transport capacity of coptisine in MDCK cells expressing the variants of hOCT1-P341L or hOCT2-A270S was significantly higher than that in wild-type (WT) cells with the Clint(Vmax/Km) of 379 ± 7.4 and 433 ± 5.7 μl/mg protein/min, respectively.3. The above data indicate that the tested alkaloids are potent inhibitors, and coptisine, jatrorrhizine, epiberberine and berberrubine are substrates of hOCT1, hOCT2 and/or hOCT3 with high affinity. In addition, the variants (OCT1-P341L and OCT2-A270S) possess higher transport capacity to coptisine than WT hOCTs.
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影响因子：
4.5
作者：
Mei-juan Tu;Siyuan Sun;Kai Wang;Xue-feng Peng;Ruihan Wang;Li-ping Li-Li-ping-Li-1651122038;S. Zeng;Hui Zhou;
通讯作者：
Mei-juan Tu;Siyuan Sun;Kai Wang;Xue-feng Peng;Ruihan Wang;Li-ping Li-Li-ping-Li-1651122038;S. Zeng;Hui Zhou;
DOI：
10.1007/978-3-319-23793-0
发表时间：
2016
期刊：
Springer International Publishing
影响因子：
--
作者：
S. Gautron;E. Schlatter
通讯作者：
S. Gautron;E. Schlatter
DOI：
10.4268/cjcmm20101523
发表时间：
2010-08
期刊：
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
影响因子：
--
作者：
Liang Wang;Xiaoli Ye;Xuegang Li;Zhu Chen;Xiaodan Chen;Ying Gao;Zhongqi Zhao;Wenwen Huang;Xin Chen;Jun Yi
通讯作者：
Liang Wang;Xiaoli Ye;Xuegang Li;Zhu Chen;Xiaodan Chen;Ying Gao;Zhongqi Zhao;Wenwen Huang;Xin Chen;Jun Yi
DOI：
--
发表时间：
2006-04
期刊：
Yao xue xue bao = Acta pharmaceutica Sinica
影响因子：
--
作者：
Jian Sun;Ji-sheng Ma;Jin Jin-Jin;Huai-sheng Wang;Qing-hui Wen;Hong-gui Zhang;Qiu-li Zhou
通讯作者：
Jian Sun;Ji-sheng Ma;Jin Jin-Jin;Huai-sheng Wang;Qing-hui Wen;Hong-gui Zhang;Qiu-li Zhou
影响因子：
13.5
作者：
Nies, Anne T.;Koepsell, Hermann;Schaeffeler, Elke
通讯作者：
Schaeffeler, Elke