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Transepithelial transport

The in vitro system we have been using to study the transepithelial transport is cultured Madin-Darby canine kidney (MDCK) epithelial cells (11). When cultured on microporous polycarbonate filters (Transwell, Costar, Cambridge, MA), MDCK cells will develop into monolayers mimicking the mucosal epithelium (11). When these cells reach confluence, tight junctions will be established between the cells, and free diffusion of solutes across the cell monolayer will be markedly inhibited. Tight junction formation can be monitored by measuring the transepithelial electrical resistance (TEER) across the cell monolayers. In Figure 1, MDCK cells were seeded at 2 X 104 cells per well in Transwells (0.4 p pore size) as described previously. TEER and 14C-sucrose transport were measured daily. To determine 14C-sucrose... [Pg.121]

Figure 1. The correlation of transepithelial electrical resistance (TEER) with the transepithelial transport of 14C-sucrose in MDCK cell monolayers grown on microporous filters. Figure 1. The correlation of transepithelial electrical resistance (TEER) with the transepithelial transport of 14C-sucrose in MDCK cell monolayers grown on microporous filters.
In series with a desolvation energy barrier required to disrupt aqueous solute hydrogen bonds [14], the lipid bilayer offers a practically impermeable barrier to hydrophilic solutes. It follows that significant transepithelial transport of water-soluble molecules must be conducted paracellularly or mediated by solute translocation via specific integral membrane proteins (Fig. 6). Transcellular permeability of lipophilic solutes depends on their solubility in GI membrane lipids relative to their aqueous solubility. This lumped parameter, membrane permeability,... [Pg.171]

Tubular reabsorption is considered passive when each of the steps in transepithelial transport takes place without the expenditure of energy. In other words, the movement of a given substance is from an area of high concentration to an area of low concentration by way of passive diffusion. Water is passively reabsorbed from the tubules back into the peritubular capillaries. [Pg.317]

Fotopoulos, G., A. Harari, P. Michetti, D. Trono, G. Pantaleo, and J. Kraehenbuhl. Transepithelial transport of HIV-1 by M cells is receptor-mediated., Proc. Natl. Acad. Sci. USA 2002, 99, 9410-9414... [Pg.84]

Walter, E., Kissel, T., Heterogeneity in the human intestinal cell line Caco-2 leads to differences in transepithelial transport, Eur. J. [Pg.121]

Walter, E., Kissel, T., Reers, M., Dickneite, G., Hoffmann, D., Stuber, W., Transepithelial transport properties of peptidomimetic thrombin inhibitors in monolayers of a human intestinal cell line (Caco-2) and their correlation to in vivo data, Pharm. Res. 1995, 32, 360-365. [Pg.123]

S. J., Goldenberg, S., Wiliams, C., Pasatan, I., Gottesman, M. M., Handler, J., Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epifhelia, J. Biol. Chem. 1989, 264, 14880-14884. [Pg.124]

Heylen, P., van den Mooter, G., Kinget, R., Drug absorption studies of prodrugs esters using the Caco-2 model evaluation of ester hydrolysis and transepithelial transport, Int. J. Pharm. 1998, 166, 45-53. [Pg.129]

Watanabe, K., et al. Studies on intestinal absorption of sulpiride (2) transepithelial transport of sulpiride across the human intestinal cell line Caco-2. Biol. Pharm. Bull. 2002, 25, 1345-1350. [Pg.272]

Swaan, P. W., et al. Enhanced transepithelial transport of peptides by conjugation to cholic acid. Bioconjug. Chem. 1997, 8, 520-525. [Pg.285]

Figure 8.2 Possible drug transport pathways across the intestinal mucosa, illustrating transcellular (1) and paracellular (2) modes of passive transport, transcytosis (3), carrier-mediated transport (4), and efflux transport (5). A combination of these routes often defines the overall transepithelial transport rate of nutrients and drugs. Figure 8.2 Possible drug transport pathways across the intestinal mucosa, illustrating transcellular (1) and paracellular (2) modes of passive transport, transcytosis (3), carrier-mediated transport (4), and efflux transport (5). A combination of these routes often defines the overall transepithelial transport rate of nutrients and drugs.
The example of amprenavir, an HIV-1 protease inhibitor, shows that intestinal metabolism can also be used as a strategy to enhance the bioavailability of compounds. In the biopharmaceutics classification system (BCS), amprenavir can be categorized as a class II compound it is poorly soluble but highly permeable [51]. Fosamprenavir, the water-soluble phosphate salt of amprenavir, on the other hand, shows poor transepithelial transport. However, after oral administration of fosamprenavir, this compound is metabolized into amprenavir in the intestinal lumen and in the enterocytes mainly by alkaline phosphatases, resulting in an increased intestinal absorption [51, 174],... [Pg.186]

Keywords Transepithelial Transport Tight junction Lateral intercellular space Estrogen ATP Calcium... [Pg.339]

The theoretical model that best describes regulation of transepithelial transport is derived from the Ussing-Zerahn equivalent electrical circuit model of ion transport theory [57] (Figure 15.1B). The model predicts that epithelia are organized as a layer(s) of confluent cells, where plasma membranes of neighboring cells come into close contact and functionally occlude the intercellular space. Accordingly, molecules can move across epithelia either through the cells... [Pg.341]

Gorodeski GI, Romero MF, Hopfer U, Rorke E, Utian WH, and Eckert RL [ 1994] Human uterine cervical epithelial cells grown on permeable support—a new model for the study of differentiation and transepithelial transport. Differentiation 56 107-118... [Pg.358]

In addition to screening molecules for intestinal absorption, Caco-2 cells have also been used to study mechanisms of drug transport. For many compounds, intestinal permeation involves a transporter to either aid or limit transepithelial transport. The value of Caco-2 cells in this type of studies is due to the fact that these cells express various membrane transporters relevant to drug absorption.1719-23,28,30 However, when interpreting results of studies that involve carrier-mediated transport, discretion, and scaling factors may be required because of the difference in expression level of transporters between in vitro and in vivo systems.12 Another important consideration in carrier-mediated transport studies is that some transport systems in Caco-2 cells may achieve maximal expression level at different days in culture.17,21,38,74 Thus, validation of Caco-2 cells for mechanistic studies should include the identification of the time for optimal expression of transporters as well as the qualitative evaluation of the transporters to establish that they are representative of the native intestinal transporters. [Pg.171]

Caco-2 cells have been valuable in the estimation of drug absorption potential, transport mechanisms, and effect of permeation enhancers on transepithelial transport.35,39,53,67-69,78-81 Owing to the sensitivity of the cells and the limited solubility of new molecular entities, Caco-2 permeability studies are routinely done with relatively low concentration of compounds. One way to increase the solubility of these compounds is to use organic solvents. The low tolerability of Caco-2 cells to organic solvents limits the use of this approach in permeability studies. [Pg.175]

Neutra, M. and Kraehenhuhl, J.P., Transepithelial transport of proteins by intestinal epithelial cells, in Biological Barriers to Protein Delivery, Audus, K.L. and Raub, T.J., Eds., Plenum Press, New York, 1993, pp. 107-129. [Pg.179]

Konishi, Y. and Shimizu, M., Transepithelial transport of ferulic acid by monocarboxylic acid transporter in Caco-2 cell monolayers, Biosci Biotechnol Biochem., 67, 856, 2003. [Pg.353]

Konishi, Y. and Kobayashi, S., Transepithelial transport of chlorogenic acid, caffeic acid, and their colonic metabolites in intestinal caco-2 cell monolayers, J. Agric. Food Chem., 52, 2518, 2004. [Pg.354]


See other pages where Transepithelial transport is mentioned: [Pg.195]    [Pg.169]    [Pg.119]    [Pg.440]    [Pg.317]    [Pg.97]    [Pg.536]    [Pg.357]    [Pg.125]    [Pg.339]    [Pg.341]    [Pg.376]    [Pg.377]    [Pg.377]    [Pg.385]    [Pg.560]    [Pg.594]    [Pg.162]    [Pg.177]    [Pg.180]    [Pg.538]   
See also in sourсe #XX -- [ Pg.317 ]

See also in sourсe #XX -- [ Pg.882 ]




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