Mechanism of dextran transport across rabbit intestinal tissue and a human colon cell-line (CACO-2).
The in vitro permeabilities of 14C labeled dextrans (10, 40, and 70 kD) were calculated from mass transport across Peyer's patches and non-patch tissues derived from rabbit jejunum, and a human colon cell line (Caco-2) grown as a monolayer on polycarbonate filters. Size distribution of dextrans did not change upon transport as judged from size exclusion chromatography. Permeabilities decreased in a size-dependent manner. Ranking of permeabilities for dextran 10 and 40 kD were: Caco-2 > non-patch tissue > Peyer's patches; while dextran 70 kD demonstrated no difference among the barriers. Tissue resistance, expressed as 1/(permeability.tissue thickness) was virtually the same in Peyer's patches and non-patch tissue, suggesting that tissue thickness and not interaction determines the difference in permeability. ATP depletion with ouabain, Na(+)-azide and 2-deoxy-D-glucose, and low temperature (4 degrees C) did not result in reduced permeabilities suggesting passive transport. The results suggest that the investigated intestinal barriers transport dextrans in a similar fashion independent of their source. However, comparison of the ratios dextran 10 kD/mannitol and PEG 900/mannitol between rabbit tissue and Caco-2 monolayers suggests Caco-2 monolayers may serve as a model to study absorption potential of potentially harmful compounds in coeliac disease, gastroenteritis, and colon carcinoma.
Rubas
W
W
Department of Pharmaceutical Sciences, Syntex Research, Palo Alto, CA 94303, USA.
Jezyk
N
N
Grass
G M
GM
D000230:Adenocarcinoma / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism; D003911:Dextrans / Q000032:analysis / Q000378:metabolism*; D004058:Diffusion; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism; D008970:Molecular Weight; D010539:Permeability; D010581:Peyer's Patches / Q000378:metabolism; D011817:Rabbits
D003911:Dextrans; D000255:Adenosine Triphosphate