BIDIRECTIONAL SMALL-INTESTINAL PERMEABILITY IN THE RAT TO SOME COMMONMARKER MOLECULES IN-VITRO

Background: The barrier properties of the small intestine were investi gated by studying the bidirectional permeability to five commonly used marker molecules. Methods: Proximal and distal small-intestinal segme nts from rats were mounted in diffusion chambers, and the permeation o f the markers H-3-mannitol (Mw 182), Cr-51-ethylenediaminetetraacetic acid (Mw 341), [mercaptopropionic acid(1), D-arginine(8)]vasopressin ( Mw 1069), fluorescein isothiocyanate (FITC)-dextran (mean Mw 3000), an d inulin (Mw 5200) was measured across the mucosa in both directions. Results: A generally increased inward (mucosa to serosa) and a decreas ed outward (serosa to mucosa) permeation of the markers was found in t he proximal to distal direction. The inward permeability showed increa sing regional differences with decreasing size of the markers. In the absence of the villous epithelium, removed by scraping the intestinal wall, 86% to 62% of the proximal and distal barrier was lost in the in ward direction but only 14% to 26% in the outward direction. Conclusio ns: The intestinal epithelial barrier is more permeable in the outward than in the inward direction, and regional permeability differences e xist in a size-dependent fashion. The results suggest two passage rout es, one for the smallest molecule, mannitol, and a second for the larg er markers in the present size range, both apparently different from t he route for macromolecules such as intact proteins.