@article {Turvill564, author = {J L Turvill and P Kasapidis and M J G Farthing}, title = {The sigma ligand, igmesine, inhibits cholera toxin andEscherichia coli enterotoxin induced jejunal secretion in the rat}, volume = {45}, number = {4}, pages = {564--569}, year = {1999}, doi = {10.1136/gut.45.4.564}, publisher = {BMJ Publishing Group}, 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{\textendash}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.CTcholera toxin5-HT5-hydroxytryptamineLTEscherichia coliheat labile enterotoxinNPYneuropeptide YPEGpolyethylene glycol 4000PESplasma electrolyte solutionSTaEscherichia coli heat stable enterotoxinVIPvasoactive intestinal polypeptide}, issn = {0017-5749}, URL = {https://gut.bmj.com/content/45/4/564}, eprint = {https://gut.bmj.com/content/45/4/564.full.pdf}, journal = {Gut} }