TY - JOUR
AU - SHIMIZU, Makoto
AB - Abstract 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. tripeptide, bioactive peptide, peptide transporter, paracellular pathway, Caco-2 cell References 1) Brantl, V., Teschmacher, H., Henschen, A., and Lottspeich, F., Novel opioid peptides derived from casein (β-casein). Hoppe-Seyler's Z. Physiol. Chem., 360, 1211-1216 (1979). 2) Maruyama, S., Nakagomi, K., Tomizuka, N., and Suzuki, H., Angiotensin-converting enzyme inhibitor derived from an enzymatic hydrolyzate of casein. Agric. Biol. Chem., 49, 1405-1409 (1985). 3) Sato, R., Noguchi, T., and Naito, H., Casein phosphopeptide (CPP) enhances calcium absorption from the ligated segment of rat small intestine. J. Nutr. Sci. Vitaminol., 32, 67-76 (1986). 4) Migliore-Samour, D., and Jolles, P., Casein, a prohormone with an immunomodulating role for the newborn. Experientia, 44, 188-193 (1988). 5) Arai, S., Osawa, T., Ohigashi, H., Yoshikawa, M., Kaminogawa, S., Watanabe, M., Ogawa, T., Okubo, K., Watanabe, S., Nishino, H., Shinohara, K., Esashi, T., and Hirahara, T., A mainstay of functional food science in Japan—History, present status, and future outlook. Biosci. Biotechnol. Biochem., 65, 1-13 (2001). 6) Yoshikawa, M., and Chiba, H. Biologically active peptides derived from food and blood proteins. In “Frontiers and New Horizons in Amino Acid Research,” ed. Takai, K., Elsevier Sci. Pub., Amsterdam, pp. 403-409 (1992). 7) Ariyoshi, Y., Angiotensin-converting enzyme inhibitors derived from food proteins. Trends Food Sci. Technol., 4, 139-144 (1993). 8) Meisel, H., Casokinins as inhibitors of angiotensin-converting enzyme. In “New Perspectives in Infant Nutrition,” eds. Renner, B., and Sawatzki, G., Thieme Medical Pub., New York, pp. 153-159 (1993). 9) Fujita, H., Yokoyama, K., and Yoshikawa, M., Classification and antihypertensive activity of angiotensin I-converting enzyme inhibitory peptides derived from food proteins. J. Food Sci., 65, 564-569 (2000). 10) Yokoyama, K., Chiba, H., and Yoshikawa, M., Peptide inhibitors for angiotensin I-converting enzyme from thermolysin digest of dried bonito. Biosci. Biotechnol. Biochem., 56, 1541-1545 (1992). 11) Nakamura, Y., Yamamoto, N., Sakai, K., and Takano, T., Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J. Dairy Sci., 78, 11253-11257 (1995). 12) Pappenheimer, J. R., Dahl, C. E., Karnovsky, M. L., and Maggio, J. E., Intestinal absorption and excretion of octapeptides composed of D-amino acids. Proc. Natl. Acad. Sci. USA, 91, 1942-1945 (1994). 13) Adson, A., Raub. T. J., Burton, P. S., Barsuhn, C. L., Hilgers, A. R., Audus, K. L., and Ho, N. F. H., Quantitative approaches to delineate paracellular diffusion in cultured epithelial cell monolayers. J. Pharm. Sci., 83, 1529-1536 (1994). 14) Shimizu, M., Tsunogai, M. and Arai, S., Transepithelial transport of oligopeptides in the human intestinal cell, Caco-2. Peptides, 18, 681-687 (1997). 15) Sai, M., Kajita, M., Tamai, I., Wakama, J., Wakamiya, T., and Tsuji, A., Adsorptive-mediated endocytosis of a basic peptide in erythrocyte-like Caco-2 cells. Am. J. Physiol., 275, G514-G520 (1998). 16) Fei, Y-J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F., Romero, M. F., Singh, S. K., Boron, W. F., and Hediger, M. A., Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature, 368, 563-566 (1994). 17) Liang, R., Fei, Y-J., Prasad, P. D., Ramamoorthy, S., Han, H., Yang-Feng, T. L., Hediger, M. A., Ganapathy, V., and Leibach, F., Human intestinal H+/peptide cotransporter. J. Biol. Chem., 270, 6456-6463 (1995). 18) Tsuji, A., and Tamai, I., Carrier-mediated intestinal transport of drugs. Pharm. Res., 13, 963-977 (1996). 19) Hidalgo, I. J., Raub, T. J., and Borchardt, R. T., Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology, 96, 736-749 (1989). 20) Hashimoto, K., and Shimizu, M., Epithelial properties of human intestinal Caco-2 cells cultured in serum-free medium. Cytotechnology, 13, 175-184 (1993). 21) Enjoh, M., Hashimoto, K., Arai, S., and Shimizu, M., Inhibitory effect of Arphamenine A on intestinal dipeptide transport. Biosci. Biotechnol. Biochem., 60, 1893-1895 (1996). 22) Dyer, J., Beechey, R. B., Gorvel, J-P., Smith, R. T., Wootton, R., and Shirazi-Beechey, S. P., Glycyl-L-Proline transport in rabbit enterocyte basolateral-membrane vesicles. Biochem. J., 269, 565-571 (1990). 23) Saito, H., and Inui, K., Dipeptide transporters in apical and basolateral membranes of the human intestinal cell line Caco-2. Am. J. Physiol., 265: G289-G294 (1993). 24) Hansen, S. H., Olsson, A., and Casanova, J. E., Wortmannin, an inhibitor of phosphoinositide 3-kinase, inhibits transcytosis in polarized epithelial cells. J. Biol. Chem., 270, 28425-28432 (1995). 25) Rose, J. M., and Audus, K. L., Receptor-mediated angiotensin II transcytosis by brain microvessel endothelial cells. Peptides, 19, 1023-1030 (1998). 26) Matthews, D. M., and Payne, J. W., Transmembrane transport of small peptides. In “Current topics in membrane and transport,” eds. Bronner, F., and Kleinzeller, A., Academic Press, New York, pp. 331-425 (1980). 27) Karbach, U., Paracellular calcium transport across the small intestine. J. Nutr., 122, 672-677 (1992). 28) Howell, S., Kenny, A. J., and Turner, A. J., A survey of membrane peptidases in two human colonic cell lines, Caco-2 and HT-29. Biochem. J., 284, 595-601 (1992). 29) Thwaites, D. T., Brown, C. D. A., Hirst, B. H., and Simmons, L., H+-coupled dipeptide (glycylsarcosine) transport across apical and basal borders of human intestinal Caco-2 cell monolayers display distinctive characteristics. Biochim. Biophys. Acta, 1151, 237-245 (1993). 30) Heymann, M., Crain-Denoyelle, A-M., Nath, S. K., and Desjeux, J-F., Quantification of protein transcytosis in the human colon carcinoma cell line Caco-2. J. Cell. Physiol., 143, 391-395 (1990). 31) Mitic, L. L., Van Itallie, C. M., and Anderson, J. M., Molecular physiology and pathophysiology of tight junctions. I. Tight junction structure and function: lessons from mutant animals and proteins. Am. J. Physiol., 279, G250-G254 (2000). 32) Nusrat, A., Turner, J. R., and Madara, J. L., Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am. J. Physiol., 279, G851-G857 (2000). 33) Madara, J. L., and Stafford, J., Interferon-γ directly affects barrier function of cultured intestinal epithelial monolayers. J. Clin. Invest., 83, 724-727 (1989). 34) Madara, J. L., and Pappenheimer, J. R., Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J. Membr. Biol., 100, 149-164 (1987). 35) Hashimoto, K., Matsunaga, N., and Shimizu, M., Effect of vegetable extracts on the transepithelial permeability of the human intestinal Caco-2 cell monolayer. Biosci. Biotechnol. Biochem., 58, 1345-1346 (1994). 36) Hashimoto, K., Kawagishi, H., Nakayama, T., and Shimizu, M., Effect of capsianoside, a diterpene glycoside, on tight-junctional permeability. Biochim. Biophys. Acta, 1323, 281-290 (1997). 37) Conradi, R. A., Wilkinson, K. F., Rush, B. D., Hilgers, A. R., Ruwart, M. J., and Burton, P. S., In vitro/in vivo models for peptide oral absorption: Comparison of Caco-2 cell permeability with rat intestinal absorption of renin inhibitory peptides. Pharm. Res., 10, 1790-1792 (1993). 38) Masuda, O., Nakamura, Y., and Takano, T., Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats. J. Nutr., 126, 3063-3068 (1996). 39) Meredith, D., and Boyd, C. A. R., Oligopeptide transport by epithelial cells. J. Membr. Biol., 145, 1-12 (1995). PDF This content is only available as a PDF. © 2002 by Japan Society for Bioscience, Biotechnology, and Agrochemistry This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) © 2002 by Japan Society for Bioscience, Biotechnology, and Agrochemistry
TI - Transepithelial Transport of the Bioactive Tripeptide, Val-Pro-Pro, in Human Intestinal Caco-2 Cell Monolayers
JF - Bioscience Biotechnology and Biochemistry
DO - 10.1271/bbb.66.378
DA - 2002-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/transepithelial-transport-of-the-bioactive-tripeptide-val-pro-pro-in-0BiGllWzAx
SP - 378
EP - 384
VL - 66
IS - 2
DP - DeepDyve
ER -