Efflux of sphingoid bases by P-glycoprotein in human intestinal Caco-2 cells
Efflux of sphingoid bases by P-glycoprotein in human intestinal Caco-2 cells
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DOI：
10.1271/bbb.68.2541
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发表时间：
2004-12-01
影响因子：
1.6
通讯作者：
Saito, M
中科院分区：
文献类型：
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作者：
Sugawara, T;Kinoshita, M;Saito, M
本研究的目的是确定源自不同饮食来源（例如哺乳动物、植物和真菌）的鞘氨醇碱是否是分化的 Caco-2 细胞（用作肠上皮细胞模型）中 P-糖蛋白的底物。在 Caco-2 细胞中，鞘氨醇（哺乳动物中最常见的鞘氨醇碱）的摄取在生理温度下显着高于顺式/反式-8-鞘氨醇、反式-4、顺式-8-鞘氨醇、9-甲基-反式-4、反式-8-鞘氨醇或鞘氨醇。维拉帕米是一种有效的 P-糖蛋白抑制剂，以剂量依赖性方式增加鞘氨醇碱（鞘氨醇除外）的细胞积累。与 1 mum 地高辛一起孵育 48 小时，导致多药耐药 (MDR)1 mRNA 上调，并减少 Caco-2 细胞中鞘氨醇碱基的积累（鞘氨醇除外）。因此，P-糖蛋白可能有助于消化道中膳食鞘脂中鞘氨醇的选择性吸收。
The aim of this study was to determine whether sphingoid bases that originated from various dietary sources, such as mammals, plants, and fungi, are substrates for P-glycoprotein in differentiated Caco-2 cells, which are used as a model of intestinal epithelial cells. In Caco-2 cells, the uptake of sphingosine, the most common sphingoid base found in mammals, was significantly higher at physiological temperatures than those of cis/trans-8-sphingenine, trans-4, cisitrans-8-sphingadienine, 9-methyl-trans-4, trans-8-sphingadienine, or sphinganine. Verapamil, a potent P-glycoprotein inhibitor, increased the cellular accumulation of sphingoid bases, except for sphingosine, in a dose-dependent manner. Incubation with 1 mum digoxin for 48 h caused up-regulation of multidrug-resistance (MDR)1 mRNA and decreased the accumulation of sphingoid bases in Caco-2 cells, except for sphingosine. Thus P-glycoprotein probably contributes to the selective absorption of sphingosine from dietary sphingolipids in the digestive tract.