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Small intestine
The sigma ligand, igmesine, inhibits cholera toxin andEscherichia coli enterotoxin induced jejunal secretion in the rat
  1. J L Turvill,
  2. P Kasapidis,
  3. M J G Farthing
  1. Digestive Diseases Research Centre, St Bartholomew’s and The Royal London School of Medicine and Dentistry, Turner Street, London E1 2AD, UK
  1. Dr Turvill.

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

    • https://doi.org/10.1136/gut.45.4.564

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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
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