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Digestive Diseases and Sciences

, Volume 47, Issue 11, pp 2531–2537 | Cite as

Role of CCKA Receptors in Postprandial Lower Esophageal Sphincter Function in Morbidly Obese Subjects

  • D.P. Hirsch
  • E.M.H. Mathus-Vliegen
  • R.H. Holloway
  • N. Fakhry
  • M. D'Amato
  • G.N.J. Tytgat
  • G.E.E. Boeckxstaens
Article

Abstract

To reduce weight, some morbidly obese patients are treated with an intragastric balloon, often resulting in increased reflux symptoms. As transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism underlying reflux and can be reduced by cholecystokinin-A (CCKA) blockade, we hypothesized that the CCKA-receptor antagonist loxiglumide could reduce gastroesophageal reflux in these subjects. Postprandial manometric studies were performed in 12 obese subjects during infusion of placebo or loxiglumide. Before balloon placement, loxiglumide did not significantly reduce the rate of TLESRs but attenuated the postprandial decrease in LES pressure. After 10 weeks of balloon treatment, loxiglumide significantly reduced the rate of TLESRs. Postprandial LES pressure was significantly increased, whereas the meal-induced decrease in LES pressure was absent. Neither loxiglumide nor balloon placement affected gastroesophageal reflux. In conclusion, CCKA receptors play an important role in post-prandial LES pressure decrease and are involved in the reflex pathway underlying the triggering of TLESRs, at least after balloon placement.

cholecystokinin obesity gastroesophageal reflux lower esophageal sphincter transient lower esophageal sphincter relaxation 

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REFERENCES

  1. 1.
    Dent J, Holloway RH, Toouli J, Dodds WJ: Mechanisms of lower oesophageal sphincter incompetence in patients with symptomatic gastroesophageal reflux. Gut 29:1020–1028, 1988Google Scholar
  2. 2.
    Dodds WJ, Dent J, Hogan WJ, Helm JF, Hauser R, Patel GK, Egide MS: Mechanisms of gastroesophageal reflux in patients with reflux esophagitis. N Engl J Med 307:1547–1552, 1982Google Scholar
  3. 3.
    Schoeman MN, Tippett M, Akkermans LMA, Dent J, Holloway RH: Mechanisms of gastroesophageal reflux in ambulant healthy human subjects. Gastroenterology 108:83–91, 1995Google Scholar
  4. 4.
    Holloway RH, Penagini R, Ireland AC: Criteria for objective definition of transient lower esophageal sphincter relaxation. Am J Physiol 268:G128–G138, 1995Google Scholar
  5. 5.
    Holloway RH, Kocyan P, Dent J: Provocation of transient lower esophageal sphincter relaxations by meals in patients with symptomatic gastroesophageal reflux. Dig Dis Sci 36:1034–1039, 1991Google Scholar
  6. 6.
    Boulant J, Fioramonti J, Dapoigny M, Bommelaer G, Bueno L: Cholecystokinin and nitric oxide in transient lower esophageal sphincter relaxation to gastric distention in dogs. Gastroenterology 107:1059–1066, 1994Google Scholar
  7. 7.
    Boulant J, Mathieu S, D'Amato M, Abergel A, Dapoigny M, Bommelaer G: Cholecystokinin in transient lower esophageal sphincter relaxation due to gastric distension in man. Gut 40:575–581, 1997Google Scholar
  8. 8.
    Clave P, Gonzalez A, Moreno A, Lopez R, Farre A, Cusso X, D'mato M, Azpiroz F, Lluis F: Endogenous cholecystokinin enhances postprandial gastroesophageal reflux in humans through extrasphincteric receptors. Gastroenterology 115:597–604, 1998Google Scholar
  9. 9.
    Boeckxstaens GE, Hirsch DP, Fakhry N, Holloway RH, D'Amato M, Tytgat GNJ: Involvement of cholecystokinin-A receptors in transient lower esophageal sphincter relaxations triggered by gastric distention. Am J Gastroenterol 93:1823–1828, 1998Google Scholar
  10. 10.
    Zerbib F, Bruley DV, Scarpignato C, Leray V, D'Amato M, Roze C, Galmiche JP: Endogenous cholecystokinin in postprandial lower esophageal sphincter function and fundic tone in humans. Am J Physiol 275:G1266–G1273, 1998Google Scholar
  11. 11.
    Trudgill NJ, Hussain FN, Moustafa M, Ajjan R, D'Amato M, Riley SA: The effect of cholecystokinin antagonism on postprandial lower oesophageal sphincter function in asymptomatic volunteers and patients with reflux disease. Aliment Pharmacol Ther 15:1357–1364, 2001Google Scholar
  12. 12.
    Hirsch DP, Mathus-Vliegen EMH, Tytgat GNJ, Boeckxstaens GEE: The reflex arch underlying TLESRs adapts to prolonged gastric distention. Gastroenterology 118:A154, 2000Google Scholar
  13. 13.
    Mittal RK, Chiareli C, Liu J, Shaker R: Characteristics of lower esophageal sphincter relaxation induced by pharyngeal stimulation with minute amounts of water. Gastroenterology 111:378–384, 1996Google Scholar
  14. 14.
    Niederau C, Heintges T, Rovati LC, Strohmeyer G: Effects of loxiglumide on gallbladder emptying in man. Gastroenterology 97:1331–1336, 1989Google Scholar
  15. 15.
    Konturek JW, Stoll R, Konturek SJ, Domschke W: Cholecystokinin in the control of gastric acid secretion in man. Gut 34:321–328, 1993Google Scholar
  16. 16.
    Jebbink MC, Lamers CB, Mooy DM, Rovati LC, Jansen JB: Effect of loxiglumide on basal and gastrin-and bombesinstimulated gastric acid and serum gastrin levels. Gastroenterology 103:1215–1220, 1992Google Scholar
  17. 17.
    Mittal RK, McCallum RW: Characteristics and frequency of transient relaxations of the lower esophageal sphincter in patients with reflux esophagitis. Gastroenterology 95:593–599, 1988Google Scholar
  18. 18.
    Holloway RH, Hongo M, Berger K, McCallum RW: Gastric distension: a mechanism for postprandial gastroesophageal reflux. Gastroenterology 89:779–784, 1985Google Scholar
  19. 19.
    Yuan SY, Brookes SJ, Costa M: Distension-evoked ascending and descending reflexes in the isolated guinea-pig stomach. J Auton Nerv Syst 62:94–102, 1997Google Scholar
  20. 20.
    Yuan S, Brookes SJ: Neuronal control of the gastric sling muscle of the guinea pig. J Comp Neur 412:669–680, 1999Google Scholar
  21. 21.
    Resin H, Stern DH, Sturdevant RAL, Isenberg JI: Effect of the C-terminal octapeptide of cholecystokinin on lower esophageal sphincter pressure in man. Gastroenterology 64:946–949, 1973Google Scholar
  22. 22.
    Katschinski M, Schirra J, Koppelberg T, Arnold R, Rovati LC, Beglinger C, Adler G: Effect of cholecystokinin-A-receptor blockade on oesophageal motility. Eur J Gastroenterol Hepatol 6:983–989, 1994Google Scholar
  23. 23.
    Schwartz GJ, McHugh PR, Moran TH: Pharmacological dissociation of responses to CCK and gastric loads in rat mechanosensitive vagal afferents. Am J Physiol 267:R303–R308, 1994Google Scholar

Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • D.P. Hirsch
    • 1
  • E.M.H. Mathus-Vliegen
    • 1
  • R.H. Holloway
    • 2
  • N. Fakhry
    • 1
  • M. D'Amato
    • 3
  • G.N.J. Tytgat
    • 1
  • G.E.E. Boeckxstaens
    • 1
  1. 1.Division of Gastroenterology and Hepatology, Meibergdreef 9AZ Academic Medical CentreAmsterdamThe Netherlands
  2. 2.Department of Gastrointestinal MedicineRoyal Adelaide HospitalAdelaideAustralia
  3. 3.Rotta Research LaboratoriumMonzaItaly

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