title: The effect of hyperosmosis on paracellular permeability in Caco-2 cell monolayers.
abstract: The intestinal epithelium is a significant barrier to oral absorption of hydrophilic compounds, and their passage through the intercellular space is restricted by the tight junctions. In this study we found that hyperosmosis is a significant factor altering paracellular transport in Caco-2 cell monolayers. Osmotic regulators, such as sodium chloride, mannitol, and raffinose, decreased transepithelial electrical resistance and enhanced lucifer yellow permeability. The effect of these osmotic regulators on Caco-2 cell monolayers was not likely to be caused by gross cytotoxicity. Although certain amino acids and oligosaccharides have been reported to have specific tight junction-modulating activity, we found that the increased paracellular permeability of Caco-2 monolayers induced by these compounds was at least partly due to the increased osmotic pressure of the test solutions. These findings provide a new potential precaution in the evaluation of paracellular permeability-modulating substances using the Caco-2 cell monolayer system.
authors.affiliation: Oral Liquid Formulation R&D Laboratories, Self Medication Business, Taisho Pharmaceutical Co., Ltd., Saitama-shi, Japan. hitoshi.inokuchi@po.rd.taisho.co.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Inokuchi
authors.forename: Takuto
authors.initials: T
authors.lastname: Takei
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Aikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D004187:Disaccharides / Q000494:pharmacology; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology / Q000633:toxicity; D009995:Osmosis; D010172:Palmitoylcarnitine / Q000494:pharmacology; D010539:Permeability; D011887:Raffinose / Q000494:pharmacology / Q000633:toxicity; D012965:Sodium Chloride / Q000494:pharmacology / Q000633:toxicity; D019108:Tight Junctions / Q000187:drug effects
chemical_list: D004187:Disaccharides; D005971:Glutamates; D007546:Isoquinolines; D010172:Palmitoylcarnitine; D008353:Mannitol; D012965:Sodium Chloride; C087758:difructose anhydride III; C017475:lucifer yellow; D011887:Raffinose