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首页> 外文期刊>Life sciences >Transport kinetics of leucine enkephalin across Caco-2 monolayers: quantitative analysis for contribution of enzymatic and transport barrier.
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Transport kinetics of leucine enkephalin across Caco-2 monolayers: quantitative analysis for contribution of enzymatic and transport barrier.

机译：亮氨酸脑啡肽跨Caco-2单层的运输动力学：定量分析酶和运输障碍的贡献。

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摘要

In this study, we determined the activities of four aminopeptidases such as aminopeptidase B (APB), M (APM), N (APN) and dipeptidylpeptidase IV (DPP IV) in Caco-2 cells and compared with those in the rat intestinal mucosae. The activities of APB, APM and APN appeared to be highest in rat small intestinal mucosa, while DPP IV activity was much higher in Caco-2 cells than that in the rat intestinal mucosa. Next the inhibitory effects of various protease inhibitors were examined in Caco-2 homogenate. Three tested inhibitors, bacitracin, amastatin and puromycin, effectively inhibited the activities of APM, APN and DPP IV except for APB. Further, we quantitatively evaluated the permeation and degradation properties of leucine enkephalin (Leu-Enk) in the presence or absence of inhibitors in Caco-2 monolayer system. Leu-Enk had a high degradation clearance (CLd) and a low permeation clearance (CLp) in Caco-2 monolayers. This finding indicates that the very rapid degradation of Leu-Enk on the apical side of Caco-2 monolayers was due to aminopeptidases. However, these protease inhibitors besides sodium glycocholate were able to reduce the CLd values markedly, thereby increasing the permeation amount of Leu-Enk across Caco-2 monolayers. In particular, amastatin significantly decreased the CLd value and increased the CLp value. This enhanced CLp value was further increased by the coadministration with an absorption enhancer, EDTA or laurylmaltoside. These findings are relevant to the oral administration of peptide drugs and to developing an efficient oral delivery system.
机译：在这项研究中，我们确定了Caco-2细胞中四种氨基肽酶（如氨基肽酶B（APB），M（APM），N（APN）和二肽基肽酶IV（DPP IV））的活性，并与大鼠肠粘膜中的活性进行了比较。大鼠小肠粘膜中APB，APM和APN的活性最高，而Caco-2细胞中DPP IV的活性要高于大鼠肠粘膜。接下来，在Caco-2匀浆中检查了各种蛋白酶抑制剂的抑制作用。除APB外，三种测试的抑制剂杆菌肽，阿马他汀和嘌呤霉素均有效抑制APM，APN和DPP IV的活性。此外，我们定量评估了Caco-2单层系统中存在或不存在抑制剂时亮氨酸脑啡肽（Leu-Enk）的渗透和降解特性。 Leu-Enk在Caco-2单层中具有较高的降解清除率（CLd）和较低的渗透清除率（CLp）。这一发现表明，在Caco-2单分子膜的顶端，Leu-Enk的迅速降解是由于氨基肽酶引起的。但是，这些蛋白酶抑制剂除甘胆酸钠外，还能够显着降低CLd值，从而增加Leu-Enk在Caco-2单层上的渗透量。特别地，阿马他汀显着降低CLd值并增加CLp值。通过与吸收促进剂，EDTA或月桂基麦芽糖苷共同给药，可进一步提高CLp值。这些发现与肽药物的口服给药以及开发有效的口服递送系统有关。

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