Abstract

The aim of this work is to study the mechanisms involved in gonyautoxins (GTXs) intestinal absorption. For this purpose, we studied the transport of GTX 2/3 epimers by intestinal epithelial cell lines (IEC-6 and Caco-2) cultured on polycarbonate filters. Specific transport was calculated by subtracting from the flux of GTX 2/3 measured at 37°C that occurring at 4°C, this being an indication of transcellular transport. The transcellular apical-to-basolateral (A-B) flux in Caco-2 cell monolayers, was greater than that in the opposite direction, suggesting the involvement of an active transport system favoring the absorption of the toxin. However, in IEC-6 cells the transcellular basolateral-to-apical (B-A) specific transport of the toxin was greater than that in the opposite direction. The A-B and B-A fluxes were, respectively, 127±26 and 205±23nmol/min, suggesting the presence of a prevalent secretive process of the toxin in IEC-6 cells. The A-B transport of GTX 2/3 epimers in Caco-2 cells, but not in IEC-6 cells, was partially Na+-dependent and significantly inhibited by adenosine. TEA and verapamil in both Caco-2 and IEC-6 cells failed to affect the A-B and B-A transport of GTX 2/3 epimers. Cyanine in IEC-6 cells, but not in Caco-2 cells, increased the A-B flux of the toxin, suggesting the involvement of the organic cation transporter in the absorption of GTX 2/3 epimers. The mitochondrial energetic uncoupler 2,4-dinitrophenol significantly inhibited the A-B and the B-A transport in both cell lines. In conclusion, IEC-6 cells secrete actively the toxins, whereas Caco-2 cells were found to absorb the toxins in a process that was inhibited in the presence of adenosine and the absorption was dependent of Na+. © 2002 Elsevier Science Ltd. All rights reserved.