Regional small-intestinal permeability in vitro to different-sized dextrans and proteins in the rat

Molecular weight-dependent passage over different regions of the rat small intestine, using different-sized proteins/peptides and fluorescein isothiocyanate-dextrans in the 1- to 70-kDa range, was studied in vitro in modified Ussing chambers. The mucosal to serosal passage was inversely related to the molecular weight. After 120 min the passage in the proximal region usually dominated, but the nonapeptide (mercaptopropionic acid1, D-arginine8)-vasopressin differed by showing a consistently higher passage in the distal region. The similar apparent permeation coefficients obtained for the two macromolecular categories of corresponding molecular weight implied that the non-degradable dextrans could be used as permeability markers reflecting the passage per se of intact proteins. Furthermore, the results indicated two different transmucosal pathways, one of low permeability for molecules > 30 kDa, in which the molecular weight was of minor importance for the passage, and another more permeable one in the 1- to 30-kDa range, in which the passage was highly influenced by the molecular weight.