Summary
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.
Similar content being viewed by others
References
Lászik GZ, Berger Z, Pap A, Tóth GK, Varró V. Course and regression of acute interstitial pancreatitis induced in rats by repeated serial subcutaneous cholecystokininoctapeptide injections. Int J Pancreatol 1989; 5: 347–358.
Murayama KM, Drew JB, Nahrwold DL, Joehl RJ. Acute edematous pancreatitis impairs pancreatic secretion in rats. Surgery 1990; 107: 302–310.
Niederau C, Niederau M, Lüthen R, Strohmeyer G, Ferrell LD, Grendell JH. Pancreatic exocrine secretion in acute experimental pancreatitis. Gastroenterology 1990; 99: 1120–1127.
Otsuki M, Tani S, Okabayashi Y, Fujii M, Nakamurra T, Fujisawa T, Koide M, Itoh H. Fasting prevents acute pancreatitis induced by cerulein in rats. Dig Dis Sci 1990; 35: 840–848.
Nordback IH, Clemens JA, Cameron JL. The role of cholecystokinin in the pathogenesis of acute pancreatitis in the isolated pancreas preparation. Surgery 1991; 109: 301–306.
Evander A, Ihse I, Lundquist I. Influence of hormonal stimulation by caerulein on acute experimental pancreatitis in the rat. Eur Surg Res 1981; 13: 257–268.
Niederau C, Liddle RA, Ferrell LD, Grendell JH. Beneficial Effects of cholecystokinin-receptor blockade and inhibition of proteolytic enzyme activity in experimental acute hemorrhagic pancreatitis in mice. J Clin Invest 1986; 78: 1056–1063.
Modlin IM, Bilchik AJ, Zucker KA, Adrian TE, Sussman J, Graham SM. Cholecystokinin augmentation of “surgical” pancreatitis. Arch Surg 1989; 124: 574–578.
Kim KH, Lee MG, Kim DG. The cholecystokinin receptor antagonist L-364,718 reduces taurocholate-induced pancreatitis in rats. Int J Pancreatol 1996; 20: 205–211.
Tomita H, Miyasaka K, Jimi A, Mishima Y, Funakoshi A. Lack of effect of cholecystokinin receptor antagonist (CR 1505) on recovery of experimental pancreatitis after pancreatic duct occlusion in rats. Pancreas 1994; 9: 638–645.
Larsen FL, Schlarman D, Andrus CC, Kaminski DL. The effect of the CCK receptor antagonist CR 1409 on bile reflux pancreatitis in the opossum. Pancreas 1991; 6: 291–297.
Niederau C, Borchard F, Luthen R, Niederau M. Early development of experimental biliary pancreatitis and its ameloriation by CCK receptor blockade. Hepato-Gastroenterology 1996; 43: 1442–1453.
Tachibana I, Shirohara H, Czako L, Akiyama T, Nakano S, Watanabe N, et al. Role of endogenous cholecystokinin and cholecystokinin A receptors in the development of acute pancreatitis in rats. Pancreas 1997; 14: 113–121.
Sjövall S, Ahrén B, Stenram U. Effects of the specific cholecystokinin antagonist L 364,718 in experimental acute pancreatitis in the rat. Eur Surg Res 1988; 20: 325–329.
Tachibana I, Watanabe N, Shirohara H, Akiyama T, Nakano S, Otsuki M. Effects of MCI-727 on pancreatic exocrine secretion and acute pancreatitis in two experimental rat models. Pancreas 1996; 12: 165–172.
Ha SS, Satake K, Hiura A. Role of endogenous and exogenous cholecystokinin in experimental acute pancreatitis induced in rats by duodenal loop technique. J Gastroenterol 1996; 31: 404–413.
Nagai T, Yamakawa T. Experimental model with bilioenteric anastomosis in rats—technique and significance. Hepato-Gastroenterology 1992; 39: 309–313.
Nylander AG, von Friesen CP, Monstein HJ, Yamada H, Chen D, Boketoft Å, et al. Increased expression of mRNA for the CCK-A receptor in pancreas and the CCK-B receptor in oxyntic mucosa after porta-caval shunting in rats. Pharmacol Toxicol 1997; 80: 147–151.
Lankisch PG, Winkler K, Bokermann M, Schmidt H, Creutzfeldt W. The influence of glucagon on acute experimental pancreatitis in the rat. Scand J Gastroenterol 1974; 9: 725–729.
Rehfeld JF. Accurate measurement of cholecystokinin in plasma. Clin Chem 1998; 44: 991–1001.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265–275.
Dahlqvist A. A method for the determination of amylase in intestinal content. Scand Clin Lab Invest 1962; 14: 145–151.
Evander A, Hederström E, Hultberg B, Ihse I. Exocrine pancreatic secretion in acute experimental pancreatitis. Digestion 1982; 24: 159–167.
Fischer H, Konturek JW, Szlachcic A, Konturek SJ, Domschke W. Plasma amino acid consumption and pancreatic secretion during and after cerulein-induced pancreatitis in rats. Int J Pancreatol 1995; 18: 127–134.
Shirohara H, Otsuki M. Plasma cholecystokinin levels in acute pancreatitis. Pancreas 1997; 14: 249–254.
Lange P, Pedersen T. Initial treatment of acute pancreatitis. Surg Gyn Obst 1983; 157: 332–334.
Kudsk KA, Campbell SM, O’Brien T. Postoperative jejunal feedings following complicated pancreatitis. Nutr Clin Pract 1990; 5: 14–17.
McClave SA, Greene LM, Snider HL, Makk LJ, Cheadle WG, Owens NA, et al. Comparison of the safety of early enteral vs parenteral nutrition in mild acute pancreatitis. J Parenter Enteral Nutr 1997; 21: 14–20.
Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg 1997; 84: 1665–1669.
Tarpila E, Larsson L, Lilja I, Ihse I. Proglumide treatment in bile-induced acute experimental pancreatitis. Int J Pancreatol 1988; 3: 195–202.
Song W, Yamaguchi H, Nakano I, Kimura T, Nawata H. Role of endogenous cholecystokinin in the regeneration of pancreatic tissue after hemorrhagic pancreatitis in rats. Fukuoka Igaku Zasshi 1996; 87: 14–22.
Sakagami J, Kataoka K, Ohta A, Nakajima T. Relationship of plasma CCK to acinar cell generation in acute pancreatitis as studied by proliferating cell nuclear antigen. Dig Dis Sci 1996; 41: 1828–1837.
Evander A, Lundquist I, Ihse I. Influence of gastrointestinal hormones on the course of acute experimental pancreatitis. Hepato-Gastroenterology 1982; 29: 161–166.
Ohlsson B, Axelson J, Sternby B, Rehfeld JF, Ihse I. Timecourse of the pancreatic changes following long-term stimulation or inhibition of the CCK-A receptor. Int J Pancreatol 1995; 18: 59–66.
Ohlsson B, Jansen, Rehfeld JF, 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: 255–261.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ohlsson, B., Axelson, J., Stenram, U. et al. Acute taurodeoxycholate-induced pancreatitis in the rat is associated with hyperCCKemia. International Journal of Pancreatology 27, 195–201 (2000). https://doi.org/10.1385/IJGC:27:3:195
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/IJGC:27:3:195