Skip to main content
Gut logoLink to Gut
. 1986 Apr;27(4):355–362. doi: 10.1136/gut.27.4.355

Effects of a pharmacological dose of cholecystokinin on bile acid kinetics and biliary cholesterol saturation in man.

R P Jazrawi, T C Northfield
PMCID: PMC1433401  PMID: 3957106

Abstract

In order to study the mechanisms influencing bile acid pool size and cholesterol saturation index of fasting gall bladder bile, eight obese volunteers were placed on a low calorie diet for six weeks, and given intramuscular injections of a pharmacological dose of cholecystokinin octapeptide (CCK-OP, 5 micrograms) at mealtimes for half that period (alternating order). During CCK-OP administration, postprandial emptying of the gall bladder (mean +/- SEM) increased from 58 +/- 11% to 82 +/- 5% (p less than 0.005), and small intestinal transit time decreased from 205 +/- 27 to 178 +/- 26 minutes (NS). Bile acid pool size decreased from 4.6 +/- 0.3 to 3.1 +/- 0.3 mmol (p less than 0.001), while fractional turnover rate for chenodeoxycholic acid increased from 0.23 +/- 0.02 to 0.36 +/- 0.03 per day (p less than 0.005), suggesting an increase in recycling frequency of the pool. Synthesis rate was unchanged (0.43 +/- 0.08 vs 0.44 +/- 0.07 mmol/day), suggesting a new steady state. The cholesterol saturation index of fasting gall bladder bile increased in all subjects from 1.3 +/- 0.1 to 1.6 +/- 0.1 (p less than 0.005). Fasting gall bladder volume was reduced from 29 +/- 4 to 20 +/- 7 ml (p less than 0.01). Fractional turnover rate on the two regimens correlated with gall bladder emptying (n = 16, r = 0.61, p less than 0.01), but not with small intestinal transit time (r = 0.07, NS). Bile acid pool size correlated with fractional turnover rate (r = -0.73, p less than 0.005) and with cholesterol saturation index (r = -0.56, p less than 0.025). These findings suggest that CCK influences bile acid kinetics and cholesterol saturation index of fasting gall bladder in man; and that these effects of CCK are mainly mediated via alterations in gall bladder emptying rather than through alterations in small intestinal transit rate.

Full text

PDF
358

Selected References

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

  1. Admirand W. H., Small D. M. The physicochemical basis of cholesterol gallstone formation in man. J Clin Invest. 1968 May;47(5):1043–1052. doi: 10.1172/JCI105794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  3. Behar J., Biancani P. Effect of cholecystokinin and the octapeptide of cholecystokinin on the feline sphincter of Oddi and gallbladder. Mechanisms of action. J Clin Invest. 1980 Dec;66(6):1231–1239. doi: 10.1172/JCI109974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bertaccini G., Agosti A. Action of caerulein on intestinal motility in man. Gastroenterology. 1971 Jan;60(1):55–63. [PubMed] [Google Scholar]
  5. Bond J. H., Jr, Levitt M. D., Prentiss R. Investigation of small bowel transit time in man utilizing pulmonary hydrogen (H2) measurements. J Lab Clin Med. 1975 Apr;85(4):546–555. [PubMed] [Google Scholar]
  6. Duane W. C. Simulation of the defect of bile acid metabolism associated with cholesterol cholelithiasis by sorbitol ingestion in man. J Lab Clin Med. 1978 Jun;91(6):969–978. [PubMed] [Google Scholar]
  7. Everson G. T., Braverman D. Z., Johnson M. L., Kern F., Jr A critical evaluation of real-time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology. 1980 Jul;79(1):40–46. [PubMed] [Google Scholar]
  8. Grundy S. M., Metzger A. L. A physiological method for estimation of hepatic secretion of biliary lipids in man. Gastroenterology. 1972 Jun;62(6):1200–1217. [PubMed] [Google Scholar]
  9. Hedner P., Rorsman G. Acceleration of the barium meal through the small intestine by the c-terminal octapeptide of cholecystokinin. Am J Roentgenol Radium Ther Nucl Med. 1972 Oct;116(2):245–248. doi: 10.2214/ajr.116.2.245. [DOI] [PubMed] [Google Scholar]
  10. Hegardt F. G., Dam H. The solubility of cholesterol in aqueous solutions of bile salts and lecithin. Z Ernahrungswiss. 1971 Apr;10(3):223–233. doi: 10.1007/BF02020933. [DOI] [PubMed] [Google Scholar]
  11. Hepner G. W. Effect of decreased gallbladder stimulation on enterohepatic cycling and kinetics of bile acids. Gastroenterology. 1975 Jun;68(6):1574–1581. [PubMed] [Google Scholar]
  12. Holzbach R. T., Marsh M., Olszewski M., Holan K. Cholesterol solubility in bile. Evidence that supersaturated bile is frequent in healthy man. J Clin Invest. 1973 Jun;52(6):1467–1479. doi: 10.1172/JCI107321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jazrawi R. P., Kupfer R. M., Bridges C., Joseph A., Northfield T. C. Assessment of gall-bladder storage function in man. Clin Sci (Lond) 1983 Aug;65(2):185–191. doi: 10.1042/cs0650185. [DOI] [PubMed] [Google Scholar]
  14. LINDSTEDT S. The turnover of cholic acid in man: bile acids and steroids. Acta Physiol Scand. 1957 Sep 17;40(1):1–9. doi: 10.1111/j.1748-1716.1957.tb01473.x. [DOI] [PubMed] [Google Scholar]
  15. Low-Beer T. S., Harvey R. F., Davies E. R., Read A. F. Abnormalities of serum cholecystokinin and gallbladder emptying in celiac disease. N Engl J Med. 1975 May 1;292(18):961–963. doi: 10.1056/NEJM197505012921807. [DOI] [PubMed] [Google Scholar]
  16. Low-Beer T. S., Heaton K. W., Pomare E. W., Read A. E. The effect of coeliac disease upon bile salts. Gut. 1973 Mar;14(3):204–208. doi: 10.1136/gut.14.3.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Low-Beer T. S., Pomare E. W. Regulation of bile salt pool size in man. Br Med J. 1973 May 12;2(5862):338–340. doi: 10.1136/bmj.2.5862.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Maudgal D. P., Kupfer R. M., Zentler-Munro P. L., Northfield T. C. Postprandial gall-bladder emptying in patients with gall stones. Br Med J. 1980 Jan 19;280(6208):141–143. doi: 10.1136/bmj.280.6208.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Northfield T. C., Hofmann A. F. Biliary lipid secretion in gallstone patients. Lancet. 1973 Apr 7;1(7806):747–748. doi: 10.1016/s0140-6736(73)92130-2. [DOI] [PubMed] [Google Scholar]
  20. Northfield T. C., Kupfer R. M., Maudgal D. P., Zentler-Munro P. L., Meller S. T., Garvie N. W., McCready R. Gall-bladder sensitivity to cholecystokinin in patients with gall stones. Br Med J. 1980 Jan 19;280(6208):143–144. doi: 10.1136/bmj.280.6208.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ondetti M. A., Pluscec J., Sabo E. F., Sheehan J. T., Williams N. Synthesis of cholecystokinin-pancreozymin. I. The C-terminal dodecapeptide. J Am Chem Soc. 1970 Jan 14;92(1):195–199. doi: 10.1021/ja00704a033. [DOI] [PubMed] [Google Scholar]
  22. Parker J. G., Beneventano T. C. Acceleration of small bowel contrast study by cholecystokinin. Gastroenterology. 1970 May;58(5):679–684. [PubMed] [Google Scholar]
  23. Ramirez M., Farrar J. T. The effect of secretin and cholecystokinin-pancreozymin on the intraluminal pressure of the jejunum in the unanesthetized dog. Am J Dig Dis. 1970 Jun;15(6):539–544. doi: 10.1007/BF02238114. [DOI] [PubMed] [Google Scholar]
  24. Read N. W., Miles C. A., Fisher D., Holgate A. M., Kime N. D., Mitchell M. A., Reeve A. M., Roche T. B., Walker M. Transit of a meal through the stomach, small intestine, and colon in normal subjects and its role in the pathogenesis of diarrhea. Gastroenterology. 1980 Dec;79(6):1276–1282. [PubMed] [Google Scholar]
  25. Roda A., Festi D., Sama C., Mazzella G., Alini R., Roda E., Barbara L. Enzymatic determination of cholesterol in bile. Clin Chim Acta. 1975 Nov 3;64(3):337–341. doi: 10.1016/0009-8981(75)90364-2. [DOI] [PubMed] [Google Scholar]
  26. Rubin B., Engel S. L., Drungis A. M., Dzelzkalns M., Grigas E. O., Waugh M. H., Yiacas E. Cholecystokinin-like activities in guinea pigs and in dogs of the C-terminal octapeptide (SQ 19,844) of cholecystokinin. J Pharm Sci. 1969 Aug;58(8):955–959. doi: 10.1002/jps.2600580810. [DOI] [PubMed] [Google Scholar]
  27. Shaffer E. A., Small D. M. Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity. J Clin Invest. 1977 May;59(5):828–840. doi: 10.1172/JCI108705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shefer S., Hauser S., Bekersky I., Mosbach E. H. Feedback regulation of bile acid biosynthesis in the rat. J Lipid Res. 1969 Nov;10(6):646–655. [PubMed] [Google Scholar]
  29. TALALAY P. Enzymic analysis of steroid hormones. Methods Biochem Anal. 1960;8:119–143. doi: 10.1002/9780470110249.ch3. [DOI] [PubMed] [Google Scholar]
  30. Thomas P. J., Hofmann A. F. Letter: A simple calculation of the lithogenic index of bile: expressing biliary lipid composition on rectangular coordinates. Gastroenterology. 1973 Oct;65(4):698–700. [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES