Comparative Study of Flux of FITC-labeled Dextran 4000 on Normal (iso)- and Hyper-osmolarity in Basal Side in Caco-2 Cell Monolayers

• Published in: DRUG METABOLISM AND PHARMACOKINETICS Vol. 18; no. 6; pp. 404 - 408
• Main Authors: Ohkubo, Rie, Tomita, Mikio, Hotta, Yoshiyuki, Nagira, Mayuko, Hayashi, Masahiro
• Format: Journal Article
• Language: English; Japanese
• Published: England Elsevier Ltd 2003; Japanese Society for the Study of Xenobiotics
• Subjects: Caco-2 cell monolayers; efflux; FITC-labeled dextran 4000; hyperosmolarity; sodium ferrocyanate; FITC-labeled dextran 4000; Caco-2 cell monolayers; hyperosmolarity; efflux; sodium ferrocyanate
• ISSN: 1347-4367; 1880-0920
• DOI: 10.2133/dmpk.18.404

We have shown previously that the flux of fluorescein isothiocyanate dextran 4000 (FD-4) is transported across the Caco-2 cell monolayers in a polarized fashion favoring the basal to apical direction under normal conditions (i.e., isotonic solution in basal side). Furthermore, FD-4 transport may occur via a process that included a certain degree of substrate specificity for polysaccharide and transcytosis. In the present study, we compared the flux of FD-4 in the basal to apical direction (efflux) and the apical to basal direction (influx) in stress conditions (i.e., hyperosmolarity in basal side) to those in normal conditions (i.e., iso-osmolarity in basal side). The efflux of FD-4 was increased by hyperosmolarity in basal side, but the influx was decreased when compared with normal conditions. Neither dextran 10,000 nor colchicine inhibited the efflux of FD-4 in hyperosmolarity conditions. The inhibition of efflux of FD-4 was observed not by S-nitroso-N-acetylpenicillamine but by sodium nitroprusside and sodium ferrocyanide. These results collectively suggest that hyperosmolarity in basal side accelerates the efflux of FD-4 across the transcellular route but not across the paracellular route in Caco-2 cell monolayers. And it is indicated that cyanide rather than nitric oxide is involved in dysfunction of the FD-4 efflux system irrespective of conditions such as normal osmolarity or hyperosmolarity.