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. 1999 Oct;45(4):564–569. doi: 10.1136/gut.45.4.564

The sigma ligand, igmesine, inhibits cholera toxin and Escherichia coli enterotoxin induced jejunal secretion in the rat

J Turvill 1, P Kasapidis 1, M Farthing 1
PMCID: PMC1727666  PMID: 10486366

Abstract

BACKGROUND—Cholera 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.
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.


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

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Figure 1  .

Figure 1  

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Effect of pretreatment with igmesine on cholera toxin (CT) induced jejunal net water secretion. Data expressed as median and interquartile range. *p<0.04 compared with CT; †p<0.02 compared with CT + 0.03 mg/kg igmesine (Kruskal-Wallis).

Figure 2  .

Figure 2  

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Effect of igmesine (1 mg/kg intravenously) on established cholera toxin induced jejunal net water secretion. Net water secretion in individual rats (n=12) is represented at 45 minutes (pre-igmesine) and at 75 minutes (post-igmesine). p<0.04 compared with cholera toxin alone (Mann-Whitney test).

Figure 3  .

Figure 3  

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Effect of the addition of igmesine (40 µg/ml) to the perfusate, on established cholera toxin induced jejunal net water secretion. Net water secretion in individual rats (n=8) is represented on equilibration at 45 minutes and after receiving 6 mg/kg igmesine, intrajejunally, at 75 minutes. p<0.002 compared with cholera toxin perfused with standard plasma electrolyte solution (Mann-Whitney test).

Figure 4  .

Figure 4  

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Effect of pretreatment with igmesine (1 mg/kg intravenously) on heat labile (LT) and heat stable (STa) enterotoxin induced jejunal net water secretion. Data expressed as median and interquartile range. †p<0.03 compared with LT; **p<0.01 compared with STa (Mann-Whitney test).

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