Effect of alpha-trinositol on secretion induced by Escherichia coli ST-toxin in rat jejunum.
OBJECTIVE
d-myo-inositol-1,2,6-trisphosphate (alpha-trinositol, PP56), is a synthetic isomer of the intracellular second messenger, d-myo-inositol-1,4,5-trisphospahate. The pharmacological actions of alpha-trinositol include potent anti-inflammatory properties and inhibition of the secretion induced by cholera toxin and obstructive ileus. In the present study, we investigated whether alpha-trinositol was able to influence the secretion induced by heat-stable ST-toxin from Escherichia coli in the rat jejunum.


METHODS
A midline abdominal incision was performed in anaesthetized male Sprague-Dawley rats and a 6-7 cm long jejunal segment was isolated with intact vascular supply and placed in a chamber suspended from a force displacement transducer connected to a Grass(R) polygraph. Intestinal net fluid transport was continuously monitored gravimetrically. Crystalline ST-toxin (120 mouse units) was introduced into the intestinal lumen and left there for the rest of the experiment. When a stable secretion was observed, alpha-trinositol (60 mg kg-1 h-1) or saline were infused during 2 h, followed by a 2-h control period.


RESULTS
alpha-Trinositol induced a significant (P < 0.001) inhibition of ST-toxin secretion within 30 min, lasting until 2 h after infusion had stopped. The agent also moderately increased (P < 0.05) net fluid absorption in normal jejunum. Mean arterial pressure (P < 0.001) and heart rate (P < 0.001) were reduced by alpha-trinositol.


CONCLUSIONS
The inhibition by alpha-trinositol of ST-toxin induced intestinal secretion is primarily secondary to inhibition of secretory mechanisms and only to lesser extent due to increased absorption. The detailed mechanisms of action have not been clarified but may involve suppression of inflammation possibly by means of cellular signal transduction.
Lahti
A-M
AM
Institution of Surgical Specialties, Sahlgrenska University Hospital, Göteborg, Sweden.
Cassuto
J
J
Yregård
L
L
Lindblom
L
L
Sinclair
R
R
Tarnow
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001427:Bacterial Toxins / Q000494:pharmacology*; D001794:Blood Pressure; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D007262:Infusions, Intravenous; D007295:Inositol Phosphates / Q000008:administration & dosage*; D007419:Intestinal Secretions / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007295:Inositol Phosphates; C034151:heat stable toxin (E coli); C059368:atrinositol