A Collagen IV Matrix Is Required for Guinea Pig Gastric Epithelial Cell Monolayers to Provide an Optimal Model of the Stomach Surface for Biopharmaceutical Screening

Kavvada, Klairi M., Murray, James G., Moore, Vanessa A., Coombes, Alan G. A. and Hanson, Peter J. (2005) A Collagen IV Matrix Is Required for Guinea Pig Gastric Epithelial Cell Monolayers to Provide an Optimal Model of the Stomach Surface for Biopharmaceutical Screening. Journal of Biomolecular Screening, 10 5: 495-507. doi:10.1177/1087057105276035


Author Kavvada, Klairi M.
Murray, James G.
Moore, Vanessa A.
Coombes, Alan G. A.
Hanson, Peter J.
Title A Collagen IV Matrix Is Required for Guinea Pig Gastric Epithelial Cell Monolayers to Provide an Optimal Model of the Stomach Surface for Biopharmaceutical Screening
Journal name Journal of Biomolecular Screening   Check publisher's open access policy
ISSN 1087-0571
Publication date 2005-08-01
Sub-type Article (original research)
DOI 10.1177/1087057105276035
Volume 10
Issue 5
Start page 495
End page 507
Total pages 12
Place of publication Danbury, Conn.
Publisher Sage Science Press
Language eng
Subject 111504 Pharmaceutical Sciences
Abstract The surface epithelial cells of the stomach represent a major component of the gastric barrier. Acell culturemodel of the gastric epithelial cell surface would prove useful for biopharmaceutical screening of new chemical entities and dosage forms. Primary cultures of guinea pig gastricmucous epithelial cellswere grown on filter inserts (Transwells®) for 3 days. Tight-junction formation, assessed by transepithelial electrical resistance (TEER) and permeability ofmannitol and fluorescein, was enhanced when collagen IV rather than collagen I was used to coat the polycarbonate filter. TEER for cells grown on collagen IV was close to that obtained with intact guinea pig gastric epithelium in vitro. Differentiation was assessed by incorporation of [3H]glucosamine into glycoprotein and by activity of NADPH oxidase, which produces superoxide. Both of these measures were greater for cells grown on filters coatedwith collagen I than for cells grown on plastic culture plates, but nomajor difference was found between cells grown on collagens I and IV. The proportion of cells, which stained positively for mucin with periodic acid Schiff reagent, was greater than 95% for all culture conditions. Monolayers grown on membranes coated with collagen IV exhibited apically polarized secretion of mucin and superoxide, and were resistant to acidification of the apical medium to pH 3.0 for 30 min. A screen of nonsteroidal anti-inflammatory drugs revealed a novel effect of diclofenac and niflumic acid in reversibly reducing permeability by the paracellular route. In conclusion, themucous cell preparation grown on collagen IV represents a good model of the gastric surface epithelium suitable for screening procedures.
Keyword Biomolecules - Analysis
Drugs - Testing
Drugs - Analysis
stomach
Gastric
mucous cell
nonsteroidal anti-inflammatory drug
Transwells
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Pharmacy Publications
 
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