The toxin of diarrheic shellfish poisoning, okadaic acid, increases intestinal epithelial paracellular permeability.
OBJECTIVE
Diarrhea associated with shellfish poisoning is poorly understood. The responsible toxin, dinophysistoxin 1, has been identified as okadaic acid, a potent phosphatase inhibitor, but its effects on intestinal epithelia have not been examined. The aim of this study was to investigate the effect of okadaic acid on intestinal epithelial function, both Cl- secretion and barrier function.


METHODS
Cultured human intestinal epithelial T84 cell monolayers were used. The effect of okadaic acid on these monolayers was assessed by measuring electrophysiological parameters, lactate dehydrogenase release, and 22Na+ and [3H]mannitol flux rates. Protein phosphorylation studies were performed to identify potentially involved proteins.


RESULTS
Okadaic acid does not directly stimulate Cl- secretion from intestinal epithelial cells. On the contrary, the response to well-characterized secretagogues is attenuated by okadaic acid. However, it does decrease transepithelial electrical resistance in a polarized fashion without inducing cytotoxicity. Sodium-mannitol flux studies suggest that the observed decrease in resistance is attributable to an increase in paracellular permeability.


CONCLUSIONS
Okadaic acid, the toxin responsible for diarrheic shellfish poisoning, does not stimulate Cl- secretion but increases the paracellular permeability of intestinal epithelia. This alteration in intestinal epithelial physiology may contribute to the diarrhea of shellfish poisoning.
Tripuraneni
J
J
Department of Medicine, University of Illinois, Chicago, USA.
Koutsouris
A
A
Pestic
L
L
De Lanerolle
P
P
Hecht
G
G
D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D017097:Electric Impedance; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D008387:Marine Toxins / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology* / Q000031:analogs & derivatives; D010766:Phosphorylation; D011714:Pyrans / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D008562:Membrane Glycoproteins; D011714:Pyrans; D019319:Okadaic Acid; C051904:dinophysistoxin 1