Satake Makoto, Enjoh Masashi, Nakamura Yasunori, Takano Toshiaki, Kawamura Yukio, Arai Soichi, Shimizu Makoto
Department of Applied Biological Chemistry, The University of Tokyo, Japan.
Biosci Biotechnol Biochem. 2002 Feb;66(2):378-84. doi: 10.1271/bbb.66.378.
Some of the food-derived tripeptides with angiotensin converting enzyme (ACE)-inhibitory activity have been reported to be hypotensive after being orally administered. The mechanism for the intestinal transport of these tripeptides was studied by using monolayer-cultured human intestinal Caco-2 cells which express many enterocyte-like functions including the peptide transporter (PepT1)-mediated transport system. Val-Pro-Pro, an ACE-inhibitory peptide from fermented milk, was used as a model tripeptide. A significant amount of intact Val-Pro-Pro was transported across the Caco-2 cell monolayer. This transport was hardly inhibited by a competitive substrate for PepT1. Since no intact Val-Pro-Pro was detected in the cells, Val-Pro-Pro apically taken by Caco-2 cells via PepT1 was likely to have been quickly hydrolyzed by intracellular peptidases, producing free Val and Pro. These findings suggest that PepT1-mediated transport was not involved in the transepithelial transport of intact Val-Pro-Pro. Paracellular diffusion is suggested to have been the main mechanism for the transport of intact Val-Pro-Pro across the Caco-2 cell monolayer.
据报道，一些具有血管紧张素转换酶（ACE）抑制活性的食物衍生三肽经口服后具有降血压作用。利用单层培养的人肠道Caco-2细胞研究了这些三肽的肠道转运机制，该细胞表达多种肠细胞样功能，包括肽转运体（PepT1）介导的转运系统。来自发酵乳的ACE抑制肽Val-Pro-Pro用作模型三肽。大量完整的Val-Pro-Pro穿过Caco-2细胞单层进行转运。这种转运几乎不受PepT1竞争性底物的抑制。由于在细胞中未检测到完整的Val-Pro-Pro，Caco-2细胞通过PepT1从顶端摄取的Val-Pro-Pro可能已被细胞内肽酶迅速水解，产生游离的Val和Pro。这些发现表明，PepT1介导的转运不参与完整Val-Pro-Pro的跨上皮转运。推测细胞旁扩散是完整Val-Pro-Pro穿过Caco-2细胞单层进行转运的主要机制。
