Article Text
Abstract
BACKGROUND Cholera toxin, andEscherichia 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.
AIMS To 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.
METHODS After 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.
RESULTS Cholera 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.
CONCLUSION The sigma ligand, igmesine, inhibits neurally mediated enterotoxigenic secretion. Its ability to inhibit established secretion makes it an agent with therapeutic potential.
- igmesine
- cholera toxin
- Escherichia coli enterotoxin
- jejunal secretion
Abbreviations used in this paper
- CT
- cholera toxin
- 5-HT
- 5-hydroxytryptamine
- LT
- Escherichia coliheat labile enterotoxin
- NPY
- neuropeptide Y
- PEG
- polyethylene glycol 4000
- PES
- plasma electrolyte solution
- STa
- Escherichia coli heat stable enterotoxin
- VIP
- vasoactive intestinal polypeptide
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Abbreviations used in this paper
- CT
- cholera toxin
- 5-HT
- 5-hydroxytryptamine
- LT
- Escherichia coliheat labile enterotoxin
- NPY
- neuropeptide Y
- PEG
- polyethylene glycol 4000
- PES
- plasma electrolyte solution
- STa
- Escherichia coli heat stable enterotoxin
- VIP
- vasoactive intestinal polypeptide