GTX 2/3 EPIMERS PERMEATE THE INTESTINE THROUGH A PARACELLULAR PATHWAY

The aim of this work was to typify the mechanisms involved in gonyautoxins intestinal permeability. For this purpose, permeability of gonyautoxins through intestinal epithelium, and their effect on transepithelial resistance was investigated in excised human jejunal segments. The isolated mucosa seg...

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Bibliographic Details
Published in:Journal of toxicological sciences 2007, Vol.32(3), pp.241-248
Main Authors: TORRES, Rafael, PIZARRO, Luciano, CSENDES, Attila, GARCÍA, Carlos, LAGOS, Néstor
Format: Article
Language:English
Subjects:
Diffusion
Diffusion Chambers, Culture
Dose-Response Relationship, Drug
Electric Impedance
Humans
Intestinal Absorption - drug effects
Intestinal Mucosa - drug effects
Intestinal Mucosa - metabolism
Isomerism
Jejunum - drug effects
Jejunum - metabolism
Kinetics
Models, Biological
Permeability
Saxitoxin - analogs & derivatives
Saxitoxin - chemistry
Saxitoxin - metabolism
Saxitoxin - toxicity
Tight Junctions - drug effects
Tight Junctions - metabolism
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Summary:The aim of this work was to typify the mechanisms involved in gonyautoxins intestinal permeability. For this purpose, permeability of gonyautoxins through intestinal epithelium, and their effect on transepithelial resistance was investigated in excised human jejunal segments. The isolated mucosa segments were mounted in a Ussing chamber and experiments performed under voltage-controlled conditions. Organic gonyautoxin cations were applied in the apical side and samples collected in the basolateral side. Results show that gonyautoxin 2/3 epimers (GTX 2/3) permeate the intestine through a paracellular pathway and, to reach the resolution of the technique we used, no evidence was found of any other transport mechanism involved in the process. A model was developed, according to which tight junctions undergo a toxin concentration and time-dependent change, while transepithelial resistance shows a modest decrease.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.32.241