THE EFFECT OF ALPHA-TRINOSITOL ON CHOLERA TOXIN-INDUCED HYPERSECRETION AND MORPHOLOGICAL-CHANGES IN PIG JEUNUM

alpha-Trinositol (D-myo-inositol 1,2,6-trisphosphate, PP56) is a novel antiinflammatory drug. This study elucidates the effect of intravenou s alpha-trinositol on basal and acute fluid transport and morphologica l changes following cholera toxin administration in pig jejunum in viv o. Using isolated jejunal tied-off loops, the fluid hypersecretory (ac cumulation) effect of different doses of cholera toxin was studied in pigs treated intravenously with saline added different doses (0, 4, 8, 16 and 32 mgXkg(-1)Xhr(-1)) of alpha-trinositol. Levels of alpha-trin ositol, as well as stereomicroscopical, light microscopical and scanni ng electron microscopical morphological studies were performed. Choler a toxin evoked a dose-dependent fluid hypersecretion. Treatment with a lpha-trinositol caused a dose-dependent inhibition of the cholera toxi n-induced fluid hypersecretion and did not affect basal fluid absorpti on. The 16 mgXkg(-1)Xhr(-1) alpha-trinositol dose gave a maximal inhib ition of 36%. Morphological studies showed only minor changes followin g 6 hr of exposure to 20 mu gXloop(-1) cholera toxin. These changes co nsisted of dilation of the villus capillaries, an increase of apical m embrane blebbing and a reduction of the intercellular space. Treatment with 16 mgXkg(-1)Xhr(-1) alpha-trinositol alone did not induce any mo rphological changes, and did not alter the morphological changes induc ed by cholera toxin, which caused fluid hypersecretion and only minor acute morphological changes. In conclusion, alpha-trinositol treatment reduced cholera toxin-induced fluid hypersecretion without altering b asal fluid absorption, basal morphology, or cholera toxin-induced morp hological changes in pig jejunum in vivo.