Quantitative Approaches To Delineate Paracellular Diffusion in Cultured Epithelial Cell Monolayers

作者: Anthony Adson , Thomas J. Raub , Philip S. Burton , Craig L. Barsuhn , Allen R. Hilgers

DOI: 10.1002/JPS.2600831103

关键词: ExtracellularStereochemistryMembraneOrganic anionParacellular transportTranscellularBiophysicsPassive transportChemistryMonolayerTight junctionPharmaceutical Science

摘要: When using cultured cell monolayers to determine the mechanism of transcellular diffusion molecules, it may be important identify fraction that moves through paracellular route or passively diffuses tight junctions. We characterized apparent diameter junctional pore in a variety epithelial (Caco-2, MDCK, alveolar). Using hydrophilic extracellular permeants varying molecular radii and charge (neutral, anionic, cationic, zwitterionic), rate-determining steps factors were quantitatively delineated by model for size-restricted within negative electrostatic field force. Protonated amines permeated pores faster than their neutral images while organic anions slower. With increasing size influence diminished. This approach was used quantify relationship between permeant radius transepithelial electrical resistance analyze changes as function pharmacological perturbation, such use absorption promoters adjuvants.

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