Transport of a Novel Angiotensin-I-Converting Enzyme Inhibitory Peptide Ala-His-Leu-Leu Across Human Intestinal Epithelial Caco-2 Cells
文献类型： 外文期刊
作者： Li, Ying 1 ; Zhao, Jiangtao 1 ; Liu, Xiaoli 1 ; Xia, Xiudong 1 ; Wang, Ying 1 ; Zhou, Jianzhong 1 ;
作者机构： 1.Jiangsu Acad Agr Sci, Inst Agr Prod Proc, 50 Zhongling St, Nanjing 210014, Peoples R China
关键词： Ala-His-Leu-Leu;Caco-2 cell monolayer;transport;intestinal absorption mechanism;antihypertensive peptide
期刊名称：JOURNAL OF MEDICINAL FOOD （ 影响因子：2.786； 五年影响因子：2.969 ）
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收录情况： SCI
摘要： The transport behavior and absorption mechanism of Ala-His-Leu-Leu (AHLL) intestinal absorption in Caco-2 cell monolayers were clarified systemically. The safe absorptive concentration of AHLL was 200 mu g/mL, which was determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The permeation of AHLL was concentration dependent in a bidirectional transfer and reached a plateau at 90 min. The efflux ratio was above 0.5, suggesting that AHLL was absorbed by both active transport and passive diffusion. The apparent permeability coefficients (Papp) of AHLL both from the apical (AP) to basolateral (BL) side (PappAB) and from the BL to AP side (PappBA) decreased when the temperature was lowered from 37 degrees C to 4 degrees C. The uptake of AHLL was more at pH 7.4 than at other pHs. Both verapamil and (E)-3-[[[3-[2-(7-chloro-2-quinolinyl) ethenyl] phenyl]-[[(3-dimethyl amino)-3-oxopropyl] thio] methyl] thio]-propanoic acid (MK571) inhibited the absorption of AHLL, indicating that P-glycoprotein and multi-drug resistant proteins (MRPs) were all involved in AHLL secretion, especially multi-drug resistant protein 2 (MRP2). AHLL was transported through both trans-and paracellular pathways across the Caco-2 cell monolayer. This work first elucidates the AHLL absorption mechanism in Caco-2 cells and provides the basis for future studies on the improvement of bioavailability.
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