The University of Southampton
University of Southampton Institutional Repository

Influence of morphometric factors on quantitation of paracellular permeability of intestinal epithelia in vitro

Influence of morphometric factors on quantitation of paracellular permeability of intestinal epithelia in vitro
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 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
intestinal permeability, morphometric analysis, paracellular permeability, drug absorption, caco-2 cells
0724-8741
767-773
Collett, Andrew
ad03f98a-46a3-41a1-b979-fa47a0fd45cc
Walker, David
b94e6f46-ec02-4b5b-a726-67c0aafc9f94
Sims, Erika
edb096ba-5eb7-4d1e-8973-82ec54de56e9
He, Yan‐Ling
885a7e1a-8e77-4bee-8628-ddc4aa470197
Speers, Peter
028399e4-9e72-4e6d-b8fb-098d1190379e
Ayrton, John
1d0921cc-3d7c-4b4e-aea3-4b3129f97d56
Rowland, Malcolm
680cad77-67d7-4b71-a794-c745e64def7c
Warhurst, Geoffrey
74a5cea0-c1b9-4086-a780-0b4c5595ad0e
Collett, Andrew
ad03f98a-46a3-41a1-b979-fa47a0fd45cc
Walker, David
b94e6f46-ec02-4b5b-a726-67c0aafc9f94
Sims, Erika
edb096ba-5eb7-4d1e-8973-82ec54de56e9
He, Yan‐Ling
885a7e1a-8e77-4bee-8628-ddc4aa470197
Speers, Peter
028399e4-9e72-4e6d-b8fb-098d1190379e
Ayrton, John
1d0921cc-3d7c-4b4e-aea3-4b3129f97d56
Rowland, Malcolm
680cad77-67d7-4b71-a794-c745e64def7c
Warhurst, Geoffrey
74a5cea0-c1b9-4086-a780-0b4c5595ad0e

Collett, Andrew, Walker, David, Sims, Erika, He, Yan‐Ling, Speers, Peter, Ayrton, John, Rowland, Malcolm and Warhurst, Geoffrey (1997) Influence of morphometric factors on quantitation of paracellular permeability of intestinal epithelia in vitro. Pharmaceutical Research, 14 (6), 767-773. (doi:10.1023/A:1012154506858). (PMID:9210195)

Record type: Article

Abstract

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

Full text not available from this repository.

More information

Published date: June 1997
Keywords: intestinal permeability, morphometric analysis, paracellular permeability, drug absorption, caco-2 cells
Organisations: Medical Education

Identifiers

Local EPrints ID: 359214
URI: https://eprints.soton.ac.uk/id/eprint/359214
ISSN: 0724-8741
PURE UUID: 097aaffb-a2e0-422f-bfc0-3d5f7ce49d4c

Catalogue record

Date deposited: 23 Oct 2013 12:46
Last modified: 18 Jul 2017 03:22

Export record

Altmetrics

Contributors

Author: Andrew Collett
Author: David Walker
Author: Erika Sims
Author: Yan‐Ling He
Author: Peter Speers
Author: John Ayrton
Author: Malcolm Rowland
Author: Geoffrey Warhurst

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×