Influence of morphometric factors on quantitation of paracellular permeability of intestinal epithelia in vitro.
OBJECTIVE
The relative contribution of the small and large intestine to paracellular absorption is a subject of some controversy. Direct comparison of paracellular permeability in different epithelia is complicated 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 ileum, 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 approximately 3 fold greater (91 m/cm2) than that measured in ileal villi, colonic surface and crypt cells or Caco-2 monolayers (34-37 m/cm2). However, when the relative contributions of the crypts and villi was taken into account there was no significant difference in the mean lp per mucosal area for the three epithelia studied. Using these data to correct for morphometric differences the permeabilities of a range of small hydrophilic molecules (atenolol, D-PheAsp and PEG oligomers MW 282-634) was measured. Permeability of rat ileum and colon were virtually identical for all compounds studied. In contrast, Caco-2 monolayers showed a significantly lower permeability than intestinal tissues with the difference increasing markedly with molecular size.


CONCLUSIONS
These studies suggest the importance of accounting for morphological variation when comparing the permeability characteristics of different epithelial systems.
Collett
A
A
Department of Medicine (University of Manchester School of Medicine), Hope Hospital, Salford, UK.
Walker
D
D
Sims
E
E
He
Y L
YL
Speers
P
P
Ayrton
J
J
Rowland
M
M
Warhurst
G
G
D000818:Animals; D001262:Atenolol / Q000378:metabolism; D001692:Biological Transport; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D003106:Colon / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D004553:Electric Conductivity; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007082:Ileum / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D011092:Polyethylene Glycols; D001262:Atenolol