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. 1987 Jun;205(6):641–648. doi: 10.1097/00000658-198706000-00005

Correlation of cholecystokinin receptors with gallbladder contractility in patients with gallstones.

J R Upp Jr, W H Nealon, P Singh, C J Fagan, A S Jonas, G H Greeley Jr, J C Thompson
PMCID: PMC1493065  PMID: 3592806

Abstract

The authors have previously identified two groups of patients with gallstones: those whose gallbladders contract the same as those of normal volunteers and show an increased sensitivity to endogenous cholecystokinin (CCK) ("contractors") and those whose gallbladders are relatively unresponsive ("noncontractors"). To define the mechanism responsible for these differences in contractility, the authors have measured CCK receptors on gallbladder muscle of patients with gallstones. Twenty-three patients with gallstones and 10 healthy volunteers (controls) fasted overnight. Simultaneous plasma samples for radioimmunoassay of CCK release and ultrasonographic measurements of gallbladder volume were obtained before and at intervals for 60 minutes after ingestion of Lipomul. Patients with gallstones had cholecystectomy, and CCK receptors were determined on cell membranes from gallbladder specimens by use of radiolabeled analogs of CCK-8-SO4. Histologic sections were graded for the degree of inflammation and scarring. Thirteen patients with gallstones were identified as contractors and 10 as noncontractors. Basal gallbladder volumes were not significantly different between patients in either group. The total integrated output of CCK for contractors was 1.6 +/- 0.2 ng X min/ml compared with 5.5 +/- 1.2 ng X min/ml for controls, while the integrated output for noncontractors was 11.1 +/- 2.1 ng X min/ml. Contractors had a higher number of CCK-binding sites (27.6 +/- 6.8 fmol/mg protein) than did noncontractors (4.8 +/- 1.0 fmol/mg protein). CCK receptors in gallbladders of all patients with gallstones correlated closely with gallbladder motility (y = 1.149, x = 0.624, r = 0.7, p less than 0.001). Although contractors had more mild inflammation and scarring, 40% of noncontractors had mild inflammation and scarring; there was no correlation. A decrease in CCK receptors may be an early event in the pathogenesis of gallstone formation by causing a decrease in gallbladder motility in some patients.

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Selected References

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

  1. Braverman D. Z., Johnson M. L., Kern F., Jr Effects of pregnancy and contraceptive steroids on gallbladder function. N Engl J Med. 1980 Feb 14;302(7):362–364. doi: 10.1056/NEJM198002143020702. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Everson G. T., McKinley C., Lawson M., Johnson M., Kern F., Jr Gallbladder function in the human female: effect of the ovulatory cycle, pregnancy, and contraceptive steroids. Gastroenterology. 1982 Apr;82(4):711–719. [PubMed] [Google Scholar]
  4. Fisher R. S., Stelzer F., Rock E., Malmud L. S. Abnormal gallbladder emptying in patients with gallstones. Dig Dis Sci. 1982 Nov;27(11):1019–1024. doi: 10.1007/BF01391749. [DOI] [PubMed] [Google Scholar]
  5. Forgacs I. C., Maisey M. N., Murphy G. M., Dowling R. H. Influence of gallstones and ursodeoxycholic acid therapy on gallbladder emptying. Gastroenterology. 1984 Aug;87(2):299–307. [PubMed] [Google Scholar]
  6. Fridhandler T. M., Davison J. S., Shaffer E. A. Defective gallbladder contractility in the ground squirrel and prairie dog during the early stages of cholesterol gallstone formation. Gastroenterology. 1983 Oct;85(4):830–836. [PubMed] [Google Scholar]
  7. Fried G. M., Ogden W. D., Swierczek J., Greeley G. H., Jr, Rayford P. L., Thompson J. C. Release of cholecystokinin in conscious dogs: correlation with simultaneous measurements of gallbladder pressure and pancreatic protein secretion. Gastroenterology. 1983 Nov;85(5):1113–1119. [PubMed] [Google Scholar]
  8. Gomez G., Lluis F., Guo Y. S., Greeley G. H., Jr, Townsend C. M., Jr, Thompson J. C. Bile inhibits release of cholecystokinin and neurotensin. Surgery. 1986 Aug;100(2):363–368. [PubMed] [Google Scholar]
  9. Griffen W. O., Jr, Bivins B. A., Rogers E. L., Shearer G. R., Liebschutz D., Lieber A. Cholecystokinin cholecystography in the diagnosis of gallbladder disease. Ann Surg. 1980 May;191(5):636–640. doi: 10.1097/00000658-198005000-00016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holzbach R. T. Gallbladder stasis: consequence of long-term parenteral hyperalimentation and risk factor for cholelithiasis. Gastroenterology. 1983 May;84(5 Pt 1):1055–1058. [PubMed] [Google Scholar]
  11. Ingelfinger F. J. Digestive disease as a national problem. V. Gallstones. Gastroenterology. 1968 Jul;55(1):102–104. [PubMed] [Google Scholar]
  12. Khalil T., Walker J. P., Wiener I., Fagan C. J., Townsend C. M., Jr, Greeley G. H., Jr, Thompson J. C. Effect of aging on gallbladder contraction and release of cholecystokinin-33 in humans. Surgery. 1985 Sep;98(3):423–429. [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. LaMorte W. W., Schoetz D. J., Jr, Birkett D. H., Williams L. F., Jr The role of the gallbladder in the pathogenesis of cholesterol gallstones. Gastroenterology. 1979 Sep;77(3):580–592. [PubMed] [Google Scholar]
  15. Lennon F., Feeley T. M., Clanachan A. S., Scott G. W. Effects of histamine receptor stimulation on diseased gallbladder and cystic duct. Gastroenterology. 1984 Aug;87(2):257–262. [PubMed] [Google Scholar]
  16. Lilja P., Fagan C. J., Wiener I., Inoue K., Watson L. C., Rayford P. L., Thompson J. C. Infusion of pure cholecystokinin in humans. Correlation between plasma concentrations of cholecystokinin and gallbladder size. Gastroenterology. 1982 Jul;83(1 Pt 2):256–261. [PubMed] [Google Scholar]
  17. Lonovics J., Devitt P., Rayford P. L., Thompson J. C. Actions of VIP, somatostatin, and pancreatic polypeptide on gallbladder tension and CCK-stimulated gallbladder contraction in vitro. Surg Forum. 1979;30:407–409. [PubMed] [Google Scholar]
  18. Lonovics J., Guzman S., Devitt P., Hejtmancik K. E., Suddith R. L., Rayford P. L., Thompson J. C. Release of pancreatic polypeptide in humans by infusion of cholecystokinin. Gastroenterology. 1980 Nov;79(5 Pt 1):817–822. [PubMed] [Google Scholar]
  19. 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]
  20. Nahrwold D. L., Rose R. C., Ward S. P. Abnormalities in gallbladder morphology and function in patients with cholelithiasis. Ann Surg. 1976 Oct;184(4):415–421. doi: 10.1097/00000658-197610000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Pellegrini C. A., Ryan T., Broderick W., Way L. W. Gallbladder filling and emptying during cholesterol gallstone formation in the prairie dog. A cholescintigraphic study. Gastroenterology. 1986 Jan;90(1):143–149. doi: 10.1016/0016-5085(86)90086-7. [DOI] [PubMed] [Google Scholar]
  23. Pomeranz I. S., Shaffer E. A. Abnormal gallbladder emptying in a subgroup of patients with gallstones. Gastroenterology. 1985 Mar;88(3):787–791. doi: 10.1016/0016-5085(85)90152-0. [DOI] [PubMed] [Google Scholar]
  24. Shaffer E. A., Small D. M. Gallstone disease: pathogenesis and management. Curr Probl Surg. 1976 Jul;13(7):3–72. doi: 10.1016/s0011-3840(76)80004-4. [DOI] [PubMed] [Google Scholar]
  25. Singh P., Rae-Venter B., Townsend C. M., Jr, Khalil T., Thompson J. C. Gastrin receptors in normal and malignant gastrointestinal mucosa: age-associated changes. Am J Physiol. 1985 Dec;249(6 Pt 1):G761–G769. doi: 10.1152/ajpgi.1985.249.6.G761. [DOI] [PubMed] [Google Scholar]
  26. Thompson J. C., Fried G. M., Ogden W. D., Fagan C. J., Inoue K., Wiener I., Watson L. C. Correlation between release of cholecystokinin and contraction of the gallbladder in patients with gallstones. Ann Surg. 1982 May;195(5):670–676. doi: 10.1097/00000658-198205000-00017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Walker J. P., Khalil T., Wiener I., Fagan C. J., Townsend C. M., Jr, Greeley G. H., Jr, Thompson J. C. The role of neurotensin in human gallbladder motility. Ann Surg. 1985 Jun;201(6):678–683. doi: 10.1097/00000658-198506000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wiener I., Inoue K., Fagan C. J., Lilja P., Watson L. C., Thompson J. C. Release of cholecystokinin in man: correlation of blood levels with gallbladder contraction. Ann Surg. 1981 Sep;194(3):321–327. doi: 10.1097/00000658-198109000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zhu X. G., Greeley G. H., Jr, Newman J., Wiener I., Fagan C. J., Thompson J. C. Correlation of in vitro measurements of contractility of the gallbladder with in vivo ultrasonographic findings in patients with gallstones. Surg Gynecol Obstet. 1985 Nov;161(5):470–472. [PubMed] [Google Scholar]

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