Skip to main content
NCBI home page
Gut logoLink to Gut
. 1993 Mar;34(3):321–328. doi: 10.1136/gut.34.3.321

Cholecystokinin in the control of gastric acid secretion in man.

J W Konturek 1, R Stoll 1, S J Konturek 1, W Domschke 1
PMCID: PMC1374135  PMID: 8472978

Abstract

This study was designed to determine the role of cholecystokinin in the control gastric acid secretion in men using loxiglumide, a specific cholecystokinin receptor blocker. Three groups of healthy subjects (A, B, and C) were used; group A--for studies with postprandial gastric secretion, group B--for studies with exogenous gastric secretagogues and group C--for 12 hour intragastric pH-metry. Cephalic phase stimulated by modified sham feeding in group A subjects increased gastric acid secretion to about 50% of pentagastrin maximum and the treatment with loxiglumide in a standard dose (20 mumol/kg iv loading dose plus infusion of 20 mumol/kg/h afterwards) failed to affect this secretion. Gastric acid response to a 5% peptone meal instilled intragastrically greatly enhanced gastric acid secretion and plasma gastrin concentration but the addition of loxiglumide in the standard dose resulted in further increase in both gastric acid and plasma gastrin responses to peptone meal. Infusion of caerulein in gradually increasing doses (15-120 pmol/kg/h) and gastrin releasing peptide (25-200 pmol/kg/h) resulted in a dose dependent stimulation of gastric acid secretion reaching about 35% and 25% of maximum attained with pentagastrin. When loxiglumide was added in a standard dose, the acid responses to caerulein and gastrin releasing peptide were further increased two to three fold attaining the peak reaching, respectively, about 100% and 50% of pentagastrin maximum. In group C subjects, 12 hour pH-metry revealed the usual increase in gastric pH after each meal in tests with placebo. Loxiglumide (1200 mg tablets tid, po) resulted in significantly lower pH after each meal and this was accompanied by significantly higher gastrin responses than in placebo tests. We conclude that cholecystokinin released by peptone meal, ordinary meals or gastrin releasing peptide exerts a potent inhibitory influence on gastric acid secretion and gastrin release in men and this inhibition involves subtype A cholecystokinin receptors.

Full text

PDF
321

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adler G., Beglinger C., Braun U., Reinshagen M., Koop I., Schafmayer A., Rovati L., Arnold R. Interaction of the cholinergic system and cholecystokinin in the regulation of endogenous and exogenous stimulation of pancreatic secretion in humans. Gastroenterology. 1991 Feb;100(2):537–543. doi: 10.1016/0016-5085(91)90227-c. [DOI] [PubMed] [Google Scholar]
  2. Corazziari E., Solomon T. E., Grossman M. I. Effect of ninety-five percent pure cholecystokinin on gastrin-stimulated acid secretion in man and dog. Gastroenterology. 1979 Jul;77(1):91–95. [PubMed] [Google Scholar]
  3. Johnson L. R., Grossman M. I. Analysis of inhibition of acid secretion by cholecystokinin in dogs. Am J Physiol. 1970 Feb;218(2):550–554. doi: 10.1152/ajplegacy.1970.218.2.550. [DOI] [PubMed] [Google Scholar]
  4. Kim C. K., Lee K. Y., Wang T., Sun G., Chang T. M., Chey W. Y. Role of endogenous cholecystokinin on vagally stimulated pancreatic secretion in dogs. Am J Physiol. 1989 Dec;257(6 Pt 1):G944–G949. doi: 10.1152/ajpgi.1989.257.6.G944. [DOI] [PubMed] [Google Scholar]
  5. Konturek J. W., Konturek S. J., Kurek A., Bogdal J., Oleksy J., Rovati L. CCK receptor antagonism by loxiglumide and gall bladder contractions in response to cholecystokinin, sham feeding and ordinary feeding in man. Gut. 1989 Aug;30(8):1136–1142. doi: 10.1136/gut.30.8.1136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Konturek S. J., Bielański W., Solomon T. E. Effects of an antral mucosectomy, L-364,718 and atropine on cephalic phase of gastric and pancreatic secretion in dogs. Gastroenterology. 1990 Jan;98(1):47–55. doi: 10.1016/0016-5085(90)91289-i. [DOI] [PubMed] [Google Scholar]
  7. Konturek S. J., Biernat J., Kwiecień N., Oleksy J. Effect of glucagon on meal-induced gastric secretion in man. Gastroenterology. 1975 Mar;68(3):448–454. [PubMed] [Google Scholar]
  8. Konturek S. J., Bilski J., Tasler J., Cieszkowski M. Role of cholecystokinin in the inhibition of gastric acid secretion in dogs. J Physiol. 1992;451:477–489. doi: 10.1113/jphysiol.1992.sp019174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Konturek S. J., Kwiecien N., Obtulowicz W., Kopp B., Oleksy J., Rovati L. Cholecystokinin in the inhibition of gastric secretion and gastric emptying in humans. Digestion. 1990;45(1):1–8. doi: 10.1159/000200218. [DOI] [PubMed] [Google Scholar]
  10. Konturek S. J., Swierczek J., Kwiecień N., Obtutowicz W., Dobrzańska M., Kopp B., Oleksy J. Gastric secretory and plasma hormonal responses to sham-feeding of varying duration in patients with duodenal ulcer. Gut. 1981 Dec;22(12):1003–1010. doi: 10.1136/gut.22.12.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lundell L., Cantor P., Sjövall M., Rehfeld J. F., Olbe L. Factors influencing the release of cholecystokinin induced by gastrin-releasing peptide in man. Scand J Gastroenterol. 1991 May;26(5):544–550. doi: 10.3109/00365529108998578. [DOI] [PubMed] [Google Scholar]
  12. Lundell L., Lindstedt G., Olbe L. Origin of gastrin liberated by gastrin releasing peptide in man. Gut. 1987 Sep;28(9):1128–1133. doi: 10.1136/gut.28.9.1128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Masclee A. A., Jansen J. B., Driessen W. M., Geuskens L. M., Lamers C. B. Effect of truncal vagotomy on cholecystokinin release, gallbladder contraction, and gallbladder sensitivity to cholecystokinin in humans. Gastroenterology. 1990 May;98(5 Pt 1):1338–1344. doi: 10.1016/0016-5085(90)90354-4. [DOI] [PubMed] [Google Scholar]
  14. Mayer E. A., Elashoff J., Mutt V., Walsh J. H. Reassessment of gastric acid inhibition by cholecystokinin and gastric inhibitory polypeptide in dogs. Gastroenterology. 1982 Nov;83(5):1047–1050. [PubMed] [Google Scholar]
  15. Merki H. S., Fimmel C. J., Walt R. P., Harre K., Röhmel J., Witzel L. Pattern of 24 hour intragastric acidity in active duodenal ulcer disease and in healthy controls. Gut. 1988 Nov;29(11):1583–1587. doi: 10.1136/gut.29.11.1583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Niederau C., Heintges T., Rovati L., Strohmeyer G. Effects of loxiglumide on gallbladder emptying in healthy volunteers. Gastroenterology. 1989 Nov;97(5):1331–1336. doi: 10.1016/0016-5085(89)91709-5. [DOI] [PubMed] [Google Scholar]
  17. Richardson C. T., Walsh J. H., Cooper K. A., Feldman M., Fordtran J. S. Studies on the role of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects. J Clin Invest. 1977 Aug;60(2):435–441. doi: 10.1172/JCI108793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Savarino V. Continuous intragastric pH monitoring: a real progress in the assessment of antisecretory drugs. Ital J Gastroenterol. 1990;22 (Suppl 2):20–23. [PubMed] [Google Scholar]
  19. Setnikar I., Chisté R., Makovec F., Rovati L. C., Warrington S. J. Pharmacokinetics of loxiglumide after single intravenous or oral doses in man. Arzneimittelforschung. 1988 May;38(5):716–720. [PubMed] [Google Scholar]
  20. Soll A. H., Amirian D. A., Park J., Elashoff J. D., Yamada T. Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short-term culture. Am J Physiol. 1985 May;248(5 Pt 1):G569–G573. doi: 10.1152/ajpgi.1985.248.5.G569. [DOI] [PubMed] [Google Scholar]
  21. Soll A. H., Amirian D. A., Thomas L. P., Reedy T. J., Elashoff J. D. Gastrin receptors on isolated canine parietal cells. J Clin Invest. 1984 May;73(5):1434–1447. doi: 10.1172/JCI111348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Stenquist B., Nilsson G., Rehfeld J. F., Olbe L. Plasma gastrin concentrations following sham feeding in duodenal ulcer patients. Scand J Gastroenterol. 1979;14(3):305–311. doi: 10.3109/00365527909179888. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES