caa a22 4500 477125913 CHVBK 20180405111649.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1012154506858 doi (NATIONALLICENCE)springer-10.1023/A:1012154506858 Influence of Morphometric Factors on Quantitation of Paracellular Permeability of Intestinal Epithelia In Vitro [Elektronische Daten] [Andrew Collett, David Walker, Erika Sims, Yan-Ling He, Peter Speers, John Ayrton, Malcolm Rowland, Geoffrey Warhurst] Purpose. 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 (1p) of ileal crypts was ≈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 1p 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. Plenum Publishing Corporation, 1997 intestinal permeability nationallicence morphometric analysis nationallicence paracellular permeability nationallicence drug absorption nationallicence Caco-2 cells nationallicence Collett Andrew Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut Walker David Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut Sims Erika Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut He Yan-Ling Department of Pharmacy, University of Manchester, Ml3 9PL, Manchester, UK aut Speers Peter Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut Ayrton John GlaxoWellcome, Greenford, Middlesex, UK aut Rowland Malcolm Department of Pharmacy, University of Manchester, Ml3 9PL, Manchester, UK aut Warhurst Geoffrey Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 767-773 0724-8741 14:6<767 1997 14 11095 https://doi.org/10.1023/A:1012154506858 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012154506858 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Collett Andrew Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut NATIONALLICENCE 700 1- Walker David Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut NATIONALLICENCE 700 1- Sims Erika Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut NATIONALLICENCE 700 1- He Yan-Ling Department of Pharmacy, University of Manchester, Ml3 9PL, Manchester, UK aut NATIONALLICENCE 700 1- Speers Peter Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut NATIONALLICENCE 700 1- Ayrton John GlaxoWellcome, Greenford, Middlesex, UK aut NATIONALLICENCE 700 1- Rowland Malcolm Department of Pharmacy, University of Manchester, Ml3 9PL, Manchester, UK aut NATIONALLICENCE 700 1- Warhurst Geoffrey Department of Medicine (, University of Manchester School of Medicine), Hope Hospital, M6 8HD, Salford, UK aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 767-773 0724-8741 14:6<767 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer