Effect of Inositol-Trisphosphate on Fluid Transport and Protein Extravasation in the Obstructed Small Bowel

Abstract

High-dose alpha-Trinositol is a potent inhibitor of fluid secretion in obstructive ileus, most probably involving an anti-inflammatory mechanism.

Effect of α‐trinositol on secretion induced byEscherichia coliST‐toxin in rat jejunum

“…This is in line with previous results showing that a similar dose of a-trinositol induced a marked vasodilator effect with reduced heart rate and cardiac index (Gardiner et al 1994) as well as reduced blood pressure (Lind et al 1994), at least in part due to the antagonistic effects of the agent on neuropeptide Y (NPY). This is however contradicted by observations made in a previous study (Lahti et al 2002) showing that a-trinositol induced a significant inhibition of net fluid secretion in the obstructed jejunum parallel to increased MAP. It cannot be ruled out that the inhibition of net fluid secretion induced by a-trinositol may to some extent have been influenced by the depressant effects of the agent on MAP, thereby reducing intestinal perfusion pressure and hence net fluid fluxes from circulation into the intestinal lumen.…”

“…It cannot be ruled out that the inhibition of net fluid secretion induced by a-trinositol may to some extent have been influenced by the depressant effects of the agent on MAP, thereby reducing intestinal perfusion pressure and hence net fluid fluxes from circulation into the intestinal lumen. This is however contradicted by observations made in a previous study (Lahti et al 2002) showing that a-trinositol induced a significant inhibition of net fluid secretion in the obstructed jejunum parallel to increased MAP. In addition, the level of fluid secretion in the saline-treated ST-toxin control group remained unchanged between 150 and 240 min post-toxin ( Fig.…”

“…3). In the case of obstructive ileus, this effect was paralleled by inhibition of the inflammationinduced oedema in the gut wall (Lahti et al 2002). In the case of obstructive ileus, this effect was paralleled by inhibition of the inflammationinduced oedema in the gut wall (Lahti et al 2002).…”

“…3). In a recent study (Lahti et al 2002), a similar dose (60 mg kg )1 h )1 ) was shown to inhibit net fluid secretion from the obstructed jejunum in vivo while a lower dose (10 mg kg )1 h )1 ) proved ineffective. In the case of obstructive ileus, this effect was paralleled by inhibition of the inflammationinduced oedema in the gut wall (Lahti et al 2002).…”

“…The effects of a-trinositol on fluid transport in the small intestine were investigated in a number of studies showing that the compound was able to induce a dosedependent inhibition of cholera secretion in the pig and rat jejunum in vivo (Nellgå rd et al 1992b, Hansen et al 1996, Tindholdt et al 1997. In a recent study, a-trinositol was also shown to inhibit the fluid losses induced by obstruction of the jejunum in rats in vivo at a dose of 60 mg kg )1 h )1 parallel to a significant inhibition of oedema formation in the obstructed gut (Lahti et al 2002). The inhibitory effects of the agent on obstructive ileus were suggested, at least in part, to be mediated through its inhibition of the release of inflammatory mediators (Tarnow et al 1996a), which are known to stimulate secretion in the small intestine (Mohajer & Ma 2000).…”