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Effect of loxiglumide (CR-1505) on bombesin- and meal-stimulated plasma cholecystokinin in man

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Summary

Cholecystokinin (CCK)-receptor antagonists have been reported to inhibit the effects of the hormone on the gastrointestinal tract. Their effect on plasma CCK levels in man has not been described.

The present study in 5 normal subjects demonstrated that i.v. infusion of the potent, specific CCK-receptor antagonist loxiglumide (CR 1505) significantly augmented plasma CCK levels during infusion of bombesin (402 pM per 30 min) and after administration of a meal (1390 pM per 300 min) when compared to the bombesin- (192 pM per 30 min) and meal- (886 pM per 300 min) stimulated CCK responses during infusion of saline. The basal plasma CCK during saline infusion (0.1 pM per 40 min) was not significantly influenced by CR 1505 (−1.8 pM per 40 min).

Thus, both enteral (meal) and parenteral (bombesin) stimulation of CCK secretion are augmented by CCK-receptor blockade.

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References

  1. Jansen JBMJ, Lamers CBHW (1983) Radioimmunoassay of cholecystokinin in human tissue and plasma. Clin Chim 131: 305–316

    Google Scholar 

  2. Hopman WPM, Kerstens PJSM, Jansen JBMJ, Rosenbusch G, Lamers CBHW (1985) The effect of graded physiologic doses of cholecystokinin on gallbladder contraction measured by ultrasonography; determination of treshold, dose-response relationships and comparison with intraduodenal bilirubin output. Gastroenterology 88: 1242–1247

    Google Scholar 

  3. Jansen JBMJ, Lamers CBHW (1987) Molecular forms of cholecystokinin in plasma from normal and gastrectomized human subjects following a fat meal. Peptides 8: 801–805

    Google Scholar 

  4. Becker HD, Werner M, Schafmayer A (1984) Release of radioimmunologic cholecystokinin in human subjects. Am J Surg 147: 124–128

    Google Scholar 

  5. Beglinger C, Fried M, Whitehouse I, Jansen JB, Lamers CB, Gyr K (1985) Pancreatic enzyme response to a liquid meal and to hormonal stimulation. Correlation with plasma secretion and cholecystokinin levels. J Clin Invest 75: 1471–1476

    Google Scholar 

  6. Cantor P (1986) Evaluation of a radioimmunoassay for cholecystokinin in human plasma. Scand J Clin Lab Invest 46: 213–221

    Google Scholar 

  7. Liddle RA, Goldfine ID, Williams JA (1984) Bioassay of plasma cholecystokinin in rats: Effects of food, trypsin inhibitor and alcohol. Gastroenterology 87: 542–549

    Google Scholar 

  8. Green GM, Lyman RL (1972) Feedback regulation of pancreatic enzyme secretion as a mechanism for trypsin inhibitor-induced hypersecretion in rats. Proc Soc Exp Biol Med 140: 6–12

    Google Scholar 

  9. Ise I, Lilja P (1970) Effects of intestinal amylase and trypsin on pancreatic secretion in the pig. Scand J Gastroenterol 14: 1009–1013

    Google Scholar 

  10. Ihse I, Lilja P, Lundquist I (1977) Feedback regulation of pancreatic enzyme secretion by intestinal trypsin in man. Digestion 15: 303–308

    Google Scholar 

  11. Slaff J, Jacobson D, Tillman CR, Carrington CH, Toskes Ph (1984) Protease specific suppression of pancreatic exocrine secretion. Gastroenterology 87: 44–52

    Google Scholar 

  12. Green G, Hasset ES (1977) Effect of bile duct obstruction on pancreatic enzyme secretion and intestinal proteolytic enzyme activity in rats. Dig Dis Sci 22: 437–444

    Google Scholar 

  13. Brand SJ, Morgan RGH (1982) Stimulation of pancreatic secretion and growth in the rat after feeding cholestyramine. Gastroenterology 83: 851–859

    Google Scholar 

  14. Gomez G, Lluis F, Draviam EJ, Greeley GH, Thompson JC (1986) Cholestyramine, a bile salt sequestrent, increases release of cholecystokinin and pancreatic protein secretion in dogs. Dig Dis Sci 31: 1131

    Google Scholar 

  15. Koop I, Fellgiebel A, Koop H, Schafmayer A, Arnold R (1988) Effect of cholestyramine on plasma cholecystokinin and pancreatic polypeptide levels, and exocrine secretion. Eur J Clin Invest 18: 517–523

    Google Scholar 

  16. Dlugosz J, Fölsch UR, Creutzfeldt W (1985) Inhibition of intraduodenal trypsin does not stimulate exocrine pancreatic secretion in man. Digestion 26: 197–204

    Google Scholar 

  17. Krawisz BR, Miller LJ, DiMagno EP, Go VLW (1980) In the absence of nutrients, pancreatic-biliary secretions in the jejunum do not exert feedback control of human pancreatic or gastric functions. J Lab Clin Med 95: 13–18

    Google Scholar 

  18. Adler G, Müllenhoff A, Bozkurt T, Göke B, Koop I, Arnold R (1988) Comparison of the effect of single and repeated administration of a protease inhibitor (Camostate) on pancreatic secretion in man. Scand J Gastroenterol 23: 158–162

    Google Scholar 

  19. Schlaff JI, Wolfe MM, Toskes PhP (1985) Elevated plasma cholecystokinin levels in pancreatic exocrine impairment: Evidence to support feedback regulation. J Lab Clin Med 105: 282–285

    Google Scholar 

  20. Owyang CH, May D, Louie DS (1986) Trypsin suppression of pancreatic enzyme secretion. Differential effect on cholecystokinin release and enteropancreatic reflex. Gastroenterology 91: 637–644

    Google Scholar 

  21. Jansen JBMJ, Hopman WPM, Lamers CBHW (1984) Plasma cholecystokinin concentrations in patients with pancreatic insufficiency measured by sequence-specific radioimmunoassays. Dig Dis Sci 29: 1109–1117

    Google Scholar 

  22. Jansen JBMJ, Jebbink MCW, Mulders HJA, Lamers CBHW (1989) Effect of pancreatic enzyme supplementation on post-prandial plasma cholecystokinin secretion in patients with pancreatic insufficiency. Regul Pept 25: 333–342

    Google Scholar 

  23. Masclee AAM, Jansen JBMJ, Corstens FHM, Lamers CBHW (1989) Reversible gallbladder dysfunction in severe pancreatic insufficiency. Gut 30: 866–872

    Google Scholar 

  24. Funakoshi A, Nakano I, Shinozaki H, Ibayashi H, Tateishi K, Hamaoka T (1985) Low plasma cholecystokinin response after ingestion of a test meal in patients with chronic pancreatitis. Am J Gastroenterol 80: 937–940

    Google Scholar 

  25. Cantor P, Petronijevic L, Worning H (1986) Plasma cholecystokinin concentrations in patients with advanced chronic pancreatitis. Pancreas 1: 488–493

    Google Scholar 

  26. Chang RSL, Lotti V, Monaghan RL et al (1985) A potent nonpeptide cholecystokinin antagonist selective for peripheral tissues isolated from aspergillus alliaceus. Science 230: 177–179

    Google Scholar 

  27. Makovec F, Chistè R, Bani RI, Pacini MA, Setnikar I, Rovati LA (1985) New glutaramic acid derivates with potent competitive and specific cholecystokinin-antagonistic activity. Drug Res 35: 1048–1052

    Google Scholar 

  28. Jansen JBMJ, de Jong AJL, Lamers CBHW (1988) The cholecystokinin receptor antagonist CR 1409 increases plasma cholecystokinin in rats. Regul Pept 24: 209–213

    Google Scholar 

  29. Douglas BR, Jebbink MCW, Tjon A, Tham RTO, Jansen JBMJ, Lamers CBHW (1989) The effect of loxiglumide (CR-1505) on basal and bombesin stimulated gallbladder volume in man. Eur J Pharmacol 166: 307–310

    Google Scholar 

  30. Larsson LI, Goltermann N, de Magistris L (1979) Somatostatin cell processes as pathways for paracrine secretion. Science 205: 1393–1395

    Google Scholar 

  31. Soll AH, Amirian DA, Park J, Elashoff JD, Yamada T (1985) Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short-term culture. Am J Physiol 248: G569-G573

    Google Scholar 

  32. Hosotani R, Chowdhury P, McKay D, Rayford PL (1988) Mechanism by which L 364,718 regulates biological actions of CCK on pancreas. Gastroenterology 94: A 193

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Jansen, J.B.M.J., Jebbink, M.C.W., Douglas, B.R. et al. Effect of loxiglumide (CR-1505) on bombesin- and meal-stimulated plasma cholecystokinin in man. Eur J Clin Pharmacol 38, 367–370 (1990). https://doi.org/10.1007/BF00315577

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  • DOI: https://doi.org/10.1007/BF00315577

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