Acute Taurodeoxycholate-induced Pancreatitis in the Rat is Associated with HyperCCKemia

Overview

Journal Int J Pancreatol

Specialty Gastroenterology

Date 2000 Aug 22

PMID 10952401

Citations 1

Authors

B Ohlsson

J Axelson

U Stenram

J F Rehfeld

I Ihse

Affiliations

Soon will be listed here.

Abstract

Background: Cholecystokinin (CCK) has been suggested to be involved in the development and course of acute pancreatitis. In the present study we measured plasma CCK concentrations in acute experimental pancreatitis (AEP) in the rat, and evaluated the role of circulating CCK levels on the initial pancreatic damage in pancreatitis.

Methods: Endogenous hyperCCKemia was induced by surgical biliodigestive shunt (BDS) and exogenous hyperCCKemia by infusion of CCK-8S. The CCK-A receptor antagonist devazepide was used to antagonize the effect of CCK. Pancreatitis was induced by pancreatic duct infusion of sodium taurodeoxycholate 4 wk after the BDS operation or 1 wk after the start of the infusions. Nonpancreatitic sham- and BDS-operated rats, respectively, were used as control animals as were groups of otherwise untreated rats with pancreatitis. The animals were sacrificed 6 h after induction of pancreatitis. Concentrations of CCK were determined in plasma as were protein and amylase levels in the pancreas and peritoneal exudates. The extent of pancreatic necroses was assessed microscopically.

Results: Pancreatitis caused an 11-20-fold increase of circulating CCK as measured after 6 h. In pancreatitic rats with induced hyperCCKemia, there was a further marked increase of plasma CCK. Pancreatic weight and edema, protein and amylase contents, and extent of necroses were the same regardless of the level of plasma CCK. Devazepide had no influence on the studied pancreatic parameters.

Conclusion: We conclude that acute taurodeoxycholate-induced pancreatitis in the rat is associated with elevated plasma CCK concentrations. There seems, however, not to be any correlation between the degree of hyperCCKemia and the extent of initial pancreatic damage.

Citing Articles

Role of CCK and potential utility of CCK1 receptor antagonism in the treatment of pancreatitis induced by biliary tract obstruction.

Barrett T, Yan W, Freedman J, Lagaud G, Breitenbucher J, Shankley N Br J Pharmacol. 2008; 153(8):1650-8.

PMID: 18297100 PMC: 2438255. DOI: 10.1038/bjp.2008.44.

References

Niederau C, Liddle R, Ferrell L, Grendell J . Beneficial effects of cholecystokinin-receptor blockade and inhibition of proteolytic enzyme activity in experimental acute hemorrhagic pancreatitis in mice. Evidence for cholecystokinin as a major factor in the development of acute pancreatitis. J Clin Invest. 1986; 78(4):1056-63. PMC: 423760. DOI: 10.1172/JCI112661. View

Niederau C, Borchard F, Luthen R, Niederau M . Early development of experimental biliary pancreatitis and its amelioration by CCK-receptor blockade. Hepatogastroenterology. 1996; 43(12):1442-53. View

Lankisch P, WINCKLER K, Bokermann M, Schmidt H, Creutzfeldt W . The influence of glucagon on acute experimental pancreatitis in the rat. Scand J Gastroenterol. 1974; 9(8):725-9. View

Ohlsson B, Axelson J, Sternby B, Rehfeld J, Ihse I . Time-course of the pancreatic changes following long-term stimulation or inhibition of the CCK-A receptor. Int J Pancreatol. 1995; 18(1):59-66. DOI: 10.1007/BF02825422. View

Lange P, Pedersen T . Initial treatment of acute pancreatitis. Surg Gynecol Obstet. 1983; 157(4):332-4. View

Laszik G, Berger Z, Pap A, Toth G, Varro V . Course and regression of acute interstitial pancreatitis induced in rats by repeated serial subcutaneous cholecystokinin-octapeptide injections. Int J Pancreatol. 1989; 5(4):347-58. DOI: 10.1007/BF02924299. View

Ohlsson B, Jansen C, Rehfeld J, Sternby B, Ihse I, Axelson J . Biliodigestive shunt evokes hyperCCKemia and trophic effects in the rat pancreas, but not in the liver or gastrointestinal tract. Pancreas. 1997; 14(3):255-61. DOI: 10.1097/00006676-199704000-00006. View

Tarpila E, Larsson L, Lilja I, Ihse I . Proglumide treatment in bile-induced acute experimental pancreatitis. Int J Pancreatol. 1988; 3(2-3):195-202. DOI: 10.1007/BF02798931. View

Kudsk K, Campbell S, OBrien T, Fuller R . Postoperative jejunal feedings following complicated pancreatitis. Nutr Clin Pract. 1990; 5(1):14-7. DOI: 10.1177/011542659000500114. View

10.

Modlin I, Bilchik A, Zucker K, Adrian T, Sussman J, Graham S . Cholecystokinin augmentation of 'surgical' pancreatitis. Benefits of receptor blockade. Arch Surg. 1989; 124(5):574-8. DOI: 10.1001/archsurg.1989.01410050064013. View

11.

Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos C . Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg. 1998; 84(12):1665-9. View

12.

Shirohara H, Otsuki M . Plasma cholecystokinin levels in acute pancreatitis. Pancreas. 1997; 14(3):249-54. DOI: 10.1097/00006676-199704000-00005. View

13.

Sjovall S, Ahren B, Stenram U . Effects of the specific cholecystokinin antagonist L 364,718 in experimental acute pancreatitis in the rat. Eur Surg Res. 1988; 20(5-6):325-9. DOI: 10.1159/000128781. View

14.

Niederau C, Niederau M, Luthen R, Strohmeyer G, Ferrell L, Grendell J . Pancreatic exocrine secretion in acute experimental pancreatitis. Gastroenterology. 1990; 99(4):1120-7. DOI: 10.1016/0016-5085(90)90633-c. View

15.

Nordback I, Clemens J, Cameron J . The role of cholecystokinin in the pathogenesis of acute pancreatitis in the isolated pancreas preparation. Surgery. 1991; 109(3 Pt 1):301-6. View

16.

Evander A, Ihse I, Lundquist I . Influence of hormonal stimulation by caerulein on acute experimental pancreatitis in the rat. Eur Surg Res. 1981; 13(4):257-68. DOI: 10.1159/000128192. View

17.

Kim K, Lee M, Kim D . The cholecystokinin receptor antagonist L-364,718 reduces taurocholate-induced pancreatitis in rats. Int J Pancreatol. 1996; 20(3):205-11. DOI: 10.1007/BF02803770. View

18.

Tachibana I, Shirohara H, Czako L, Akiyama T, Nakano S, Watanabe N . Role of endogenous cholecystokinin and cholecystokinin-A receptors in the development of acute pancreatitis in rats. Pancreas. 1997; 14(2):113-21. DOI: 10.1097/00006676-199703000-00002. View

19.

Fischer H, Konturek J, Szlachcic A, Konturek S, Domschke W . Plasma amino acid consumption and pancreatic secretion during and after cerulein-induced pancreatitis in rats. Int J Pancreatol. 1995; 18(2):127-34. DOI: 10.1007/BF02785886. View

20.

Sakagami J, Kataoka K, Ohta A, Nakajima T . Relationship of plasma CCK to acinar cell regeneration in acute pancreatitis as studied by proliferating cell nuclear antigen. Dig Dis Sci. 1996; 41(9):1828-37. DOI: 10.1007/BF02088754. View