INFLUENCE OF MORPHOMETRIC FACTORS ON QUANTITATION OF PARACELLULAR PERMEABILITY OF INTESTINAL EPITHELIA IN-VITRO

Purpose. The relative contribution of the small and large intestine to paracellular absorption is a subject of some controversy. Direct comp arison of paracellular permeability in different epithelia is complica ted by variations in junctional density and/or the absorptive surface area. Methods. This study used a combination of morphometric analyses and in vitro absorption studies to define permeability characteristics in relation to the amount of paracellular pathway present in rat ileu m, colon and the model epithelium, Caco-2. Results. Mucosal to serosal amplification was higher in ileum (3.9) than colon (1.9) or Caco-2 (1 ). Tight junctional density (lp) of ileal crypts was' approximate to 3 fold greater (91 m/cm(2)) than that measured in ileal villi, colonic surface and crypt cells or Caco-2 monolayers (34-37 m/cm(2)). However, when the relative contributions of the crypts and villi was taken int o account there was no significant difference in the mean Ip per mucos al area for the three epithelia studied. Using these data to correct f or morphometric differences the permeabilities of a range of small hyd rophilic molecules (atenolol, D-PheAsp and PEG oligomers MW 282-634) w as measured. Permeability of rat ileum and colon were virtually identi cal for ail compounds studied. In contrast; Caco-2 monolayers showed a significantly lower permeability than intestinal tissues with the dif ference increasing markedly with molecular size. Conclusions. These st udies suggest the importance of accounting for morphological variation when comparing the permeability characteristics of different epitheli al systems.