BACKGROUNDCholera toxin, and Escherichia coli heat labile (LT) and heat stable (STa) enterotoxins induce small intestinal secretion in part by activating enteric nerves. Igmesine is a novel sigma receptor ligand that inhibits neurally mediated secretion.
AIMSTo assess the antisecretory potential of igmesine in cholera toxin, LT, and STa induced water and electrolyte secretion using an in vivo rat model of jejunal perfusion.
METHODSAfter pretreatment with igmesine, 0.03-10 mg/kg intravenously, jejunal segments of anaesthetised, adult male Wistar rats were incubated with cholera toxin (25 µg), LT (25 µg), or saline. Jejunal perfusion with a plasma electrolyte solution containing a non-absorbable marker was undertaken. In some cases 200 µg/l STa was added to the perfusate. After equilibration, net water and electrolyte movement was determined. In additional experiments rats received igmesine, intravenously or intrajejunally, after exposure to cholera toxin.
RESULTSCholera toxin induced net water secretion was inhibited by 1 mg/kg igmesine (median 120 versus 31 µl/min/g, p<0.001). LT and STa induced secretion were also inhibited by 1 mg/kg igmesine (90 versus 56, p<0.03; and 76 versus 29, p<0.01, respectively). Igmesine reduced established cholera toxin induced secretion.
CONCLUSIONThe sigma ligand, igmesine, inhibits neurally mediated enterotoxigenic secretion. Its ability to inhibit established secretion makes it an agent with therapeutic potential.


Keywords: igmesine; cholera toxin; Escherichia coli enterotoxin; jejunal secretion