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 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.
Torres
Rafael
R
Lab. Bioquímica de Membrana, Dept. de Fisiología y Biofísica, Facultad de Medicina, Universidad de Chile, Casilla 70005, Correo 7, Santiago, Chile.
Pizarro
Luciano
L
Csendes
Attila
A
García
Carlos
C
Lagos
Néstor
N
D004058:Diffusion; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007536:Isomerism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D010539:Permeability; D012530:Saxitoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism