title: Transport of the organic cations gonyautoxin 2/3 epimers, a paralytic shellfish poison toxin, through the human and rat intestinal epitheliums.
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 degrees C that occurring at 4 degrees 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 +/- 23 nmol/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(+).
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001693:Biological Transport, Active / Q000502:physiology; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008387:Marine Toxins / Q000378:metabolism*; D051381:Rats; D012530:Saxitoxin / Q000031:analogs & derivatives* / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013237:Stereoisomerism; D019789:Tetraethylammonium / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002412:Cations; D004140:Dinitrophenols; D008387:Marine Toxins; D012530:Saxitoxin; D019789:Tetraethylammonium; D012964:Sodium; D014700:Verapamil; D000241:Adenosine; C043405:gonyautoxin II