Pflügers Archiv

, Volume 417, Issue 2, pp 174–179 | Cite as

Effect of antisecretory factor on Escherichia coli STa enterotoxin-induced alkalinisation of pig jejunal acid microclimate

  • G. T. A. McEwan
  • B. Schousboe
  • E. Skadhauge
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands


The effect of challenge by Escherichia coli STa enterotoxin on pig jejunal mucosal surface pH was investigated in vivo. Exposure to STa resulted in a rapid and reversible alkalinisation (P <0.001) of the jejunal mucosa from 6.27±0.11 (5) to 6.89±0.03 (5). This action of STa is probably mediated through cyclic 3′5′-guanosine monophosphate (cGMP) since the 8-bromo analogue of cGMP induced the same effect as that observed after STa challenge. The action of STa on mucosal pH was partially inhibited by pre-administration of an antisecretory factor (ASF) preparation. The action of 8-bromo cGMP was unchanged by the presence of ASF. This implies that ASF inhibition occurs during the early stages of STa action prior to stimulation of guanylate cyclase. This effect of STa on the pig jejunal mucosal surface pH, or acid microclimate, may explain why weak acid supplementation of oral rehydration solutions can be ineffective in certain types of diarrhoeal disease.

Key words

Antisecretory factor E. coli STa enterotoxin Acid microclimate 


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  1. Beubler E (1980) Influence of vasoactive intestinal polypeptide on net water flux and cyclic adenosine 3′,5′-monophosphate formation in the rat jejunum. Naunyn Schmiedeberg's Arch Pharmacol 313: 243–247Google Scholar
  2. Beubler E, Kollar G, Saria A, Bukhave K, Rask-Madsen J (1989) Involvement of 5-hydroxytryptamine, prostaglandin E2, and cyclic adenosine monophosphate in cholera toxin-induced fluid secretion in the small intestine of the rat in vivo. Gastroenterology 96: 368–376Google Scholar
  3. Cassuto J, Jodal M, Tuttle R, Lundgren O (1981) On the role of intramural nerves in the pathogenesis of cholera toxin-induced intestinal secretion. Scand J Gastroenterol 16: 377–384Google Scholar
  4. Coupar IM (1976) Stimulation of sodium and water secretion without inhibition of glucose absorption in the rat jejunum by vasoactive intestinal peptide (VIP). Clin Exp Pharmacol Physiol 3: 615–618Google Scholar
  5. Crane JK, Hewlett EL, Weikel CS (1989) Failure of pertussis toxin to inhibit activation of guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) in the T84 cell line. Infect Immun 57: 1186–1191Google Scholar
  6. De Jonge HR (1981) Cyclic GMP-dependent protein kinase in intestinal brush-borders. Adv Cyclic Nucleotide Res 11: 315–333Google Scholar
  7. De Jonge HR (1984) The mechanism of action of Escherichia coli heatstable toxin. Biochem Soc Trans 12: 180–184Google Scholar
  8. Donowitz M, Welsh MJ (1987) Regulation of mammalian small intestinal electrolyte secretion. In: Johnson LR (ed) Physiology of the gastrointenstinal tract, 2nd edn./Raven Press, New York, pp 1351–1388Google Scholar
  9. Eklund S, Jodal M, Lundgren O (1985) The enteric nervous system participates in the secretory response to the heat-stable enterotoxins of Escherichia coli in rats and cats. Neuroscience 14: 673–681Google Scholar
  10. Eklund S, Jodal M, Lundgren O (1986) The net fluid secretion caused by cyclic 3′5′-guanosine monophosphate in the rat jejunum in vivo is mediated by a local nervous reflex. Acta Physiol Scand 128: 57–63Google Scholar
  11. Field M, Fromm D, Al-Awqati Q, Greenough WB (1972) Effect of cholera enterotoxin on ion transport across isolated ileal mucosa. J Clin Invest 51: 796–804Google Scholar
  12. Field M, Graf LH, Laird WJ, Smith PL (1978) Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci USA 75: 2800–2804Google Scholar
  13. Frantz JC, Jaso-Friedman L, Robertson DC (1984) Binding of Escherichia coli heat-stable enterotoxin to rat intestinal cells and brush border membranes. Infect Immun 43: 622–630Google Scholar
  14. Giannella RA, Drake KW (1979) Effect of purified E.coli heat-stable enterotoxin on intestinal cyclic nucleotide metabolism and fluid secretion. Infect Immun 24: 19–23Google Scholar
  15. Giannella RA, Luttrell M, Thompson M (1983) Binding of Escherichia coli heat-stable enterotoxin to receptors on rat intestinal cells. Am J Physiol 245: G492-G498Google Scholar
  16. Guerrant RL, Chen LC, Sharp GWG (1972) Intestinal adenylate cyclase activity in canine cholera: correlation with fluid accumulation. J Infect Dis 125: 377–381Google Scholar
  17. Hughes JM, Murad F, Chang B, Guerrant RL (1978) Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli. Nature 271: 755–756Google Scholar
  18. Iwatsubo T, Yuasha H, Iga T, Hanano M (1986) Effects of potential damaging agents on the microclimate pH in the rat jejunum. J Pharm Sci 75: 1162–1165Google Scholar
  19. Krebs HA, Henseleit K (1932) Untersuchungen über die Harnstoffbildung im Tierkörper. Hoppe-Seyler's Z Physiol Chem 210: 33–66Google Scholar
  20. Kuno T, Kamisaki Y, Waldman SA, Gariepy J, Schoolnik G, Murad F (1986) Characterization of the receptor for heat-stable enterotoxin from Escherichia coli in rat intestine. J Biol Chem 261: 1470–1476Google Scholar
  21. Lange S, Lönnroth I, Skadhauge E (1987) Effects of antisecretory factor in pigs. Pflügers Arch 409: 328–332Google Scholar
  22. Lönnroth I, Lange S (1984) Purification and characterization of a hormone-like factor which inhibits cholera secretion. FEBS Lett 177: 104–108Google Scholar
  23. Lönnroth I, Lange S, Skadhauge E (1988) The antisecretory factors: inducible proteins which modulate secretion in the small intestine. Comp Biochem Physiol 90A: 611–617Google Scholar
  24. Lucas ML (1977) pH or hydrogen ion in statistics? Lancet II: 826Google Scholar
  25. Lucas ML, Blair JA (1978) The magnitude and distribution of the acid microclimate in proximal jejunum and its relation to luminal acidification. Proc R Soc Lond A 200: 27–41Google Scholar
  26. Lucas ML, Lei FH, Blair JA (1980) The influence of buffer pH, glucose and sodium ion concentration on the acid microclimate in rat proximal jejunum in vitro. Pflügers Arch 385: 137–142Google Scholar
  27. Lundgren O (1988) Nervous control of intestinal fluid transport: pyhsiology and pathophysiology. Comp Biochem Physiol 90A: 603–609Google Scholar
  28. McEwan GTA, Daniel H, Fett C, Burgess MN, Lucas ML (1988) The effect of Escherichia coli STa enterotoxin and other secretagogues on mucosal surface pH of rat small intestine in vivo. Proc R Soc Lond [Biol] 234: 219–237Google Scholar
  29. McEwan GTA, Schousboe B, Skadhauge E (1990) Direct measurement of mucosal surface pH of pig jejunum in vivo. Zentralbl Veterinarmed [A]. 37: 439–444Google Scholar
  30. McKie AT, Kusel M, McEwan GTA, Lucas ML (1988) The effect of heat-stable Escherichia coli enterotoxin, theophylline and forskolin on cyclic nucleotide levels and mucosal surface (acid microclimate) pH in rat proximal jejunum in vivo. Biochim Biophys Acta 971: 325–331Google Scholar
  31. Moss J, Vaughn M (1980) Mechanism of activation of adenylate cyclase by choleragen and E. coli heat-labile enterotoxin. In: Field M Fordtran FS, Schulte SG (eds) Secretory diarrhoea. American Physiological Society, Bethesda, pp 107–126Google Scholar
  32. Murer H, Hopfer U, Kinne R (1976) Sodium/proton antiport in brushborder-membrane vesicles isolated from rat small intestine and kidney. Biochem J 154: 597–604Google Scholar
  33. Newsome PM, Burgess MN, Mullan NA (1978), Effect of Escherichia coli heat-stable enterotoxin on cyclic GMP levels in mouse intestine. Infect Immun 22: 290–291Google Scholar
  34. Nilsson O, Cassuto J, Larsson P-A, Jodal M, Lidberg P, Ahlman H, Dahlström A, Lundgren O (1981) 5-Hydroxytryptamine and cholera secretion: a histochemical and physiological study in cats. Gut 24: 532–548Google Scholar
  35. Rao MC (1985) Toxins which activate guanylate cyclase: heat-stable enterotoxins. Ciba Found Symp 112: 74–87Google Scholar
  36. Rolston DDK, Borodo MM, Kelly MJ, Dawson AM, Farthing MJG (1987) Efficacy of oral rehydration solutions in a rat model of secretory diarrhoea. J Pediatr Gastroenterol Nutr 6: 624–630Google Scholar
  37. Shimada T (1987) Factors affecting the microclimate pH in rat jejunum. J Physiol (Lond) 392: 113–127Google Scholar
  38. Tantisara MH, Jodal M, Lungren O (1990) Effects of heat-stable Escherichia coli enterotoxin on intestinal alkaline secretion and transepithelial potential difference in the rat intestines in vivo. Scand J Gastroenterol 25: 19–28Google Scholar
  39. Waldman SA, Kuno T, Kamisaki Y, Chang LY, Gariepy J, O'Hanley P, Schoolnik G, Murad F (1986) Intestinal receptor for heat-stable enterotoxin of Escherichia coli is tightly coupled to a novel form of guanylate cyclase. Infect Immun 51: 320–326Google Scholar
  40. Yeo CJ, Couse NF, Zinner MJ (1989) Serotonin and substance P stimulate intestinal secretion in the isolated perfused ileum. Surgery 105: 86–92Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • G. T. A. McEwan
    • 1
  • B. Schousboe
    • 1
  • E. Skadhauge
    • 1
  1. 1.Department of Animal Physiology and BiochemistryThe Royal Veterinary and Agricultural UniversityFrederiksberg CDenmark

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