J. Mayol et al., Effects of a tyrosine phosphatase inhibitor on chloride secretion in humanintestinal epithelia, REV ESP E D, 92(11), 2000, pp. 743-747
AIMS: transcellular chloride transport is the key event underlying epitheli
al hydration in the intestine. Little is known about the role of protein ty
rosine phosphatases in the regulation of basal and stimulated secretion in
human intestinal epithelia. The aim of our study was to investigate the eff
ects of the protein tyrosine phosphatase inhibitor sodium orthovanadate on
vectorial chloride transport in native human colon.
METHODS: an electrophysiological technique was used to measure changes in s
hort-circuit current via a dual voltage/current clamp in native human colon
mucosa and in T84 (ATCC) human intestinal cells mounted in modified Ussing
chambers.
RESULTS: orthovanadate (1 mM) added to the serosal side of native human col
on caused a net rise in short circuit current, reflecting the stimulation o
f serosal-to-mucosal chloride movement. Epithelial cells responded similarl
y to the same concentration of the compound. The stimulatory effect of orth
ovanadate was enhanced by pretreatment with the tyrosine kinase inhibitor g
enistein, but only when orthovanadate was added to the basolateral chamber.
In contrast, the synergistic interaction did not occur when epithelial cel
ls were previously exposed to the cAMP agonist forskolin.
CONCLUSIONS: we show that tyrosine phosphatases may be involved in the regu
lation of epithelial chloride transport, and that orthovanadate stimulates
secretion in the human colon.