BACKGROUND: The barrier properties of the small intestine were investigated by studying the bidirectional permeability to five commonly used marker molecules. METHODS: Proximal and distal small-intestinal segments from rats were mounted in diffusion chambers, and the permeation of the markers 3H-mannitol (Mw 182), 51Cr-ethylenediamineteraacetic acid (Mw 341), [mercaptopropionic acid], D-arginine8]-vasopressin (Mw 1069), fluorescein isothiocyanate (FITC)-dextran (mean Mw 3000), and inulin (Mw 5200) was measured across the mucosa in both directions. RESULTS: A generally increased inward (mucosa to serosa) and a decreased outward (serosa to mucosa) permeation of the markers was found in the proximal to distal direction. The inward permeability showed increasing 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 inward direction but only 14% to 26% in the outward direction. CONCLUSIONS: The intestinal epithelial barrier is more permeable in the outward than in the inward direction, and regional permeability differences exist in a size-dependent fashion. The results suggest two passage routes, one for the smallest molecule, mannitol, and a second for the larger markers in the present size range, both apparently different from the route for macromolecules such as intact proteins.
BACKGROUND: The barrier properties of the small intestine were investigated by studying the bidirectional permeability to five commonly used marker molecules. METHODS: Proximal and distal small-intestinal segments from rats were mounted in diffusion chambers, and the permeation of the markers 3H-mannitol (Mw 182), 51Cr-ethylenediamineteraacetic acid (Mw 341), [mercaptopropionic acid], D-arginine8]-vasopressin (Mw 1069), fluorescein isothiocyanate (FITC)-dextran (mean Mw 3000), and inulin (Mw 5200) was measured across the mucosa in both directions. RESULTS: A generally increased inward (mucosa to serosa) and a decreased outward (serosa to mucosa) permeation of the markers was found in the proximal to distal direction. The inward permeability showed increasing 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 inward direction but only 14% to 26% in the outward direction. CONCLUSIONS: The intestinal epithelial barrier is more permeable in the outward than in the inward direction, and regional permeability differences exist in a size-dependent fashion. The results suggest two passage routes, one for the smallest molecule, mannitol, and a second for the larger markers in the present size range, both apparently different from the route for macromolecules such as intact proteins.
Authors: Kelly M Kitchens; Rohit B Kolhatkar; Peter W Swaan; Natalie D Eddington; Hamidreza Ghandehari Journal: Pharm Res Date: 2006-11-09 Impact factor: 4.580