Gastroenterology
Volume 136, Issue 1 , Pages 299-308.e4 , January 2009

Cholera Toxin Induces Sustained Hyperexcitability in Submucosal Secretomotor Neurons in Guinea Pig Jejunum

  • Rachel M. Gwynne

      Affiliations

    • Department of Physiology, University of Melbourne, Parkville, Victoria, Australia
    • Corresponding Author InformationAddress requests for reprints to: Rachel M. Gwynne, Department of Physiology, University of Melbourne, Parkville, Vic 3010 Australia. Phone: 61-3-8344-4466; fax: 61-3-8344-5818
    • ,
  • Melina Ellis

      Affiliations

    • Department of Physiology, University of Melbourne, Parkville, Victoria, Australia
    • ,
  • Henrik Sjövall

      Affiliations

    • Institute of Medicine, Sahlgren's Academy, University of Göteborg, Göteborg, Sweden
    • ,
  • Joel C. Bornstein

      Affiliations

    • Department of Physiology, University of Melbourne, Parkville, Victoria, Australia

Received 4 July 2008 ,Accepted 25 September 2008.

References 

  1. Lundgren O. 5-Hydroxytryptamine, enterotoxins, and intestinal fluid secretion. Gastroenterology. 1998;115:1009–1012
  2. Bearcroft CP, Andre EA, Farthing MJ. In vivo effects of the 5-HT3 antagonist alosetron on basal and cholera toxin–induced secretion in the human jejunum: a segmental perfusion study. Aliment Pharmacol Ther. 1997;11:1109–1114
  3. Mourad FH, O'Donnell LJ, Dias JA, et al. Role of 5-hydroxytryptamine type 3 receptors in rat intestinal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins. Gut. 1995;37:340–345
  4. Furness JB, Alex G, Clark MJ, et al. Morphologies and projections of defined classes of neurons in the submucosa of the guinea-pig small intestine. Anat Rec A Discov Mol Cell Evol Biol. 2003;272:475–483
  5. Furness JB. The Enteric Nervous System. Boston, Mass: Blackwell Publishing; 2006;
  6. Hubel KA, Shirazi S. Human ileal ion transport in vitro: changes with electrical field stimulation and tetrodotoxin. Gastroenterology. 1982;83:63–68
  7. Banks MR, Farthing MJ, Robberecht P, et al. Antisecretory actions of a novel vasoactive intestinal polypeptide (VIP) antagonist in human and rat small intestine. Br J Pharmacol. 2005;144:994–1001
  8. Cassuto J, Jodal M, Lundgren O. The effect of nicotinic and muscarinic receptor blockade on cholera toxin induced intestinal secretion in rats and cats. Acta Physiol Scand. 1982;114:573–577
  9. Kobayashi S, Ikeda K, Suzuki M, et al. Effects of YM905, a novel muscarinic M3-receptor antagonist, on experimental models of bowel dysfunction in vivo. Jpn J Pharmacol. 2001;86:281–288
  10. Kordasti S, Sapnara M, Thomas EA, et al. Effects of cholera toxin on the potential difference and motor responses induced by distension in the rat proximal small intestine in vivo. Am J Physiol Gastrointest Liver Physiol. 2006;290:G948–G958
  11. Mourad FH, Nassar CF. Effect of vasoactive intestinal polypeptide (VIP) antagonism on rat jejunal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins. Gut. 2000;47:382–386
  12. Jiang MM, Kirchgessner A, Gershon MD, et al. Cholera toxin–sensitive neurons in guinea pig submucosal plexus. Am J Physiol. 1993;264:G86–G94
  13. Brunsson I, Fahrenkrug J, Jodal M, et al. Substance P effects on blood flow, fluid transport and vasoactive intestinal polypeptide release in the feline small intestine. J Physiol. 1995;483(Pt 3):727–734
  14. Tien XY, Wallace LJ, Kachur JF, et al. Neurokinin A increases short-circuit current across rat colonic mucosa: a role for vasoactive intestinal polypeptide. J Physiol. 1991;437:341–350
  15. Keast JR, Furness JB, Costa M. Different substance P receptors are found on mucosal epithelial cells and submucous neurons of the guinea-pig small intestine. Naunyn Schmiedebergs Arch Pharmacol. 1985;329:382–387
  16. Perdue MH, Galbraith R, Davison JS. Evidence for substance P as a functional neurotransmitter in guinea pig small intestinal mucosa. Regul Pept. 1987;18:63–74
  17. Mathison R, Davison JS. Regulation of epithelial transport in the jejunal mucosa of the guinea pig by neurokinins. Life Sci. 1989;45:1057–1064
  18. Turvill JL, Connor P, Farthing MJ. Neurokinin 1 and 2 receptors mediate cholera toxin secretion in rat jejunum. Gastroenterology. 2000;119:1037–1044
  19. Chambers JD, Bornstein JC, Sjovall H, et al. Recurrent networks of submucous neurons controlling intestinal secretion: a modeling study. Am J Physiol Gastrointest Liver Physiol. 2005;288:G887–G896
  20. Farthing MJ. Enterotoxins and the enteric nervous system: a fatal attraction. Int J Med Microbiol. 2000;290:491–496
  21. Cassuto J, Fahrenkrug J, Jodal M, et al. Release of vasoactive intestinal polypeptide from the cat small intestine exposed to cholera toxin. Gut. 1981;22:958–963
  22. Carey HV, Cooke HJ. Submucosal nerves and cholera toxin–induced secretion in guinea pig ileum in vitro. Dig Dis Sci. 1986;31:732–736
  23. Banks MR, Golder M, Farthing MJ, et al. Intracellular potentiation between two second messenger systems may contribute to cholera toxin induced intestinal secretion in humans. Gut. 2004;53:50–57
  24. Burleigh DE, Banks MR. Stimulation of intestinal secretion by vasoactive intestinal peptide and cholera toxin. Auton Neurosci. 2007;133:64–75
  25. Jodal M, Holmgren S, Lundgren O, et al. Involvement of the myenteric plexus in the cholera toxin–induced net fluid secretion in the rat small intestine. Gastroenterology. 1993;105:1286–1293
  26. Pan H, Gershon MD. Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine. J Neurosci. 2000;20:3295–3309
  27. Vanner S, Jiang MM, Surprenant A. Mucosal stimulation evokes vasodilation in submucosal arterioles by neuronal and nonneuronal mechanisms. Am J Physiol. 1993;264:G202–G212
  28. Vanner S, Macnaughton WK. Submucosal secretomotor and vasodilator reflexes. Neurogastroenterol Motil. 2004;16(Suppl 1):39–43
  29. Gwynne RM, Bornstein JC. Synaptic transmission at functionally identified synapses in the enteric nervous system: roles for both ionotropic and metabotropic receptors. Curr Neuropharmacol. 2007;5:1–17
  30. Bornstein JC, Costa M, Furness JB. Intrinsic and extrinsic inhibitory synaptic inputs to submucous neurones of the guinea-pig small intestine. J Physiol. 1988;398:371–390
  31. Larsson MH, Sapnara M, Thomas EA, et al. Pharmacological analysis of components of the change in transmural potential difference evoked by distension of rat proximal small intestine in vivo. Am J Physiol Gastrointest Liver Physiol. 2008;294:G165–G173
  32. Lomax AE, Bertrand PP, Furness JB. Identification of the populations of enteric neurons that have NK1 tachykinin receptors in the guinea-pig small intestine. Cell Tissue Res. 1998;294:27–33
  33. Jenkinson KM, Morgan JM, Furness JB, et al. Neurons bearing NK(3) tachykinin receptors in the guinea-pig ileum revealed by specific binding of fluorescently labelled agonists. Histochem Cell Biol. 1999;112:233–246
  34. Johnson PJ, Bornstein JC. Neurokinin-1 and -3 receptor blockade inhibits slow excitatory synaptic transmission in myenteric neurons and reveals slow inhibitory input. Neuroscience. 2004;126:137–147
  35. Johnson PJ, Bornstein JC, Burcher E. Roles of neuronal NK1 and NK3 receptors in synaptic transmission during motility reflexes in the guinea-pig ileum. Br J Pharmacol. 1998;124:1375–1384
  36. Xia Y, Hu HZ, Liu S, et al. Clostridium difficile toxin A excites enteric neurones and suppresses sympathetic neurotransmission in the guinea pig. Gut. 2000;46:481–486
  37. Gwynne RM, Thomas EA, Goh SM, et al. Segmentation induced by intraluminal fatty acid in isolated guinea-pig duodenum and jejunum. J Physiol. 2004;556:557–569
  38. Lundgren O. Enteric nerves and diarrhoea. Pharmacol Toxicol. 2002;90:109–120
  39. Bertrand PP, Kunze WA, Furness JB, et al. The terminals of myenteric intrinsic primary afferent neurons of the guinea-pig ileum are excited by 5-hydroxytryptamine acting at 5-hydroxytryptamine-3 receptors. Neuroscience. 2000;101:459–469
  40. Kirchgessner AL, Tamir H, Gershon MD. Identification and stimulation by serotonin of intrinsic sensory neurons of the submucosal plexus of the guinea pig gut: activity-induced expression of Fos immunoreactivity. J Neurosci. 1992;12:235–248
  41. Monro RL, Bertrand PP, Bornstein JC. ATP and 5-HT are the principal neurotransmitters in the descending excitatory reflex pathway of the guinea-pig ileum. Neurogastroenterol Motil. 2002;14:255–264
  42. Neal KB, Bornstein JC. Mapping 5-HT inputs to enteric neurons of the guinea-pig small intestine. Neuroscience. 2007;145:556–567
  43. Reed DE, Barajas-Lopez C, Cottrell G, et al. Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons. J Physiol. 2003;547:531–542

 The authors disclose the following: Supported by the National Health and Medical Research Council of Australia project number 400053.

PII: S0016-5085(08)01793-9

doi: 10.1053/j.gastro.2008.09.071

Gastroenterology
Volume 136, Issue 1 , Pages 299-308.e4 , January 2009

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