Effects of short-term administration of the CCK receptor antagonist, KSG-504, on regeneration of pancreatic acinar cells in acute pancreatitis in rats
Tóm tắt
Cholecystokinin (CCK) receptor antagonists have been reported on have an inhibitory effect on acute experimental pancreatitis, but their long-term administration is also reported to block pancreatic regeneration. We examined whether the short-term administration of KSG-504 )KSG), a synthetic CCK-A receptor antagonist, inhibited the regeneration of pancreatic acinar cells after ethionine-induced acute pancreatitis in rats. KSG (50 mg/kg), given 12 times by subcutaneous injection at 6-h intervals, prevented the reduction of protein, amylase, and trypsinogen levels, and the DNA content of the pancreas and facilitated the recovery of these values. Ornithine decarboxylase activity in pancreatic tissue and a 5-bromo-2′-deoxyuridine labeling study indicated that DNA synthesis was accelerated in rats treated with KSG. These findings suggest that the short-term administration of KSG inhibits the development of ethionine-induced acute pancreatitis and facilitates the regeneration of acinar cells.
Tài liệu tham khảo
Solomon TE. Regulation of exocrine pancreatic cell proliferation and enzyme synthesis. In: Johnson LR (ed) Physiology of the gastrointestinal tract. New York: Raven, 1981;873–892.
Göke B, Printz H, Adler G, et al. Endogenous CCK release and pancreatic growth in rats after feeding a proteinase inhibitor (Camostate). Pancreas 1986;32:509–515.
Watanapa P, Efa EF, Beardshell K. Inhibitory effect of a cholecystokinin antagonist on the proliferative response of the pancreas to pancreatobiliary diversion. Gut 1991;32:1049–1054.
Bamba T, Ishizuka Y, Hosoda S. Effect of intrinsic CCK and CCK antagonist on pancreatic growth and pancreatic enzyme secretion in pancreaticobiliary diversion rats. Dig Dis Sci 1993; 38:653–659.
Rosewicz S, Lewis LD, Liddle RA. Effect of cholecystokinin on pancreatic ornithine decarboxylase gene expression. Am J Pysiol 1988;255:G818-G821.
Mainz DL, Black O, Webster PD. Hormonal control of pancreatic growth. J Clin Invest 1973;52:2300–2304.
Haarstad H, Petersen H. Short-and long-term effects of secretin and a cholecystokinin-like peptide on pancreatic growth and synthesis of RNA and polyamines. Scand J Gastroenterol 1989; 24:721–732.
Niederau C, Liddle RA, Ferell LD, et al. Beneficial effect of cholecystokinin-receptor blockade and inhibition of proteolytic enzyme activity in experimental acute hemorrhagic pancratitis in mice. J Clin Invest 1986;78:1056–1063.
Tachibana I, Kataoka K, Imoto M, et al. Effect of a new cholecystokinin antagonist KSG-504 on caerulein-induced acute pancreatitis in rats (in Japanese with English abstract). Suizou (J Jpn Paner Soc) 1992;7:440–447.
Tani S, Itoh H, Koide M, et al. Involvement of endogenous cholecystokinin in the development of acute pancreatitis induced by closed duodenal loop. Pancreas 1993;8:109–115.
Okumura Y, Bamba T, Shintani Y, et al. Effect of KSG-504, a new synthetic cholecystokinin receptor antagonist on ethionine-induced acute pancreatitis in rats (in Japanese with English abstract). Nippon Shokakibyo Gakkai Zassh (Jpn J Gastroenterol) 1993;90:3032–3040.
Jurkowska G, Grondin G, Masse S, et al. Soybean trypsin inhibitor and cerulein accelerate recovery of cerulein-induced pancreatitis in rats. Gastroenterology 1992;102:550–562.
Jukowska G, Grondin G, Morisset J. Involvement of endogenous cholecystokinin in pancreatic regulation after cerulein-induced acute pancreatitis. Pancreas 1992;7:295–304.
Moriyoshi Y, Shiratori K, Takeuchi T, Watanabe S. A new CCK-A antagonist, KSG-504, administered intraduodenally, inhibits pancreatic secretion in rats. Pancreas 1994;9:225–229.
Niikawa J, Shin S, Omachi H, et al. Study on pancreatic degeneration and regeneration in rat pancreatic damage induced by two doses of DL-ethionine (in Japanese with English abstract). Suizou (J Jpn Paner Soc) 1987;2:86–98.
Lowry OH, Rosenbrough N, Farr AL, Randal RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;93:265–275.
Ceska M, Birath K, Brown B. A new and rapid method for the clinical determination of alpha-amylase activities in human serum and urine. Clin Chem Acta 1969;26:437–444.
Erlanger BF, Kokowasky N, Cohen W. The preparation and properties of two new chromogenic substrates of trypsin. Arch Biochem Biophys 1961;95:271–278.
Anderson KJ, Skagen DW. Fluorometric determination of DNA in fixed tissue using ethidium bromide. Anal Biochem 1977;83:703–708.
Hashimura E, Shimizu F, Nishino T, et al. Production of rabbit antibody specific for amino-terminal residues of cholecystokinin octapeptide (CCK-8) by selective suppression of cross-reactive antibody response. J Immunol Methods 1981;47:249–258.
Beaven MA, Wilcox G, Terpstra GH. A microprocedure for the measurement of14CO2 release from [14C] carboxy-labeled aminoacids. Anal Biochem 1978;72:248–254.
Steigerwalt RW, Williams JA. Characterization of cholecystokinin receptors on rat pancreatic membrane. Endocrinology 1981;109:1746–1753.
Niederau C, Niderau M, Luthen R, et al. Pancreatic exocrine secretion in acute experimental pancreatitis. Gastroenterology 1990;99:1120–1127.
Nijdo T, Nonaka Y, Mutsukawa H, et al. Effect of CR-1505 in caerulein-induced pancreatitis. In: Japanese Society of Gut Hormones (ed) Proceedings of the gut hormone conference, Tokyo: Igaku Tosho Shuppan, 1990;172–180.
Beckh K, Göke R, Ruff W, et al. CCK receptor antagonist loxiglumide alters uptake of CCK in perfused liver and pancreatic acini of the rat. Digestion 1991;48:98–103.
Logsdon CD. Stimulation of pancreatic acinar cell growth by CCK, epidermal growth factor, and insulin in vitro. Am J Physiol 1986;251:G487-G489.
Chen D, Monstein HJ, Nylander AG, Hakanson R. Gastrin does not stimulate the growth of the rat pancreas. Digestion 1993;54:269.
Scemama JL, Vries LD, Pradayrol L, et al. Cholecystokinin and gastrin peptides stimulate ODC activity in a rat pancreatic cell line. Am J Physiol 1989;256:G846-G850.
Yu DH, Noguchi M, Zhou ZC, et al. Characterization of gastrin receptor on guinea pig pancreatic acini. Am J Physiol 1987; 253:G973-G801.
Shintani Y, Bamba T, Inoue H, et al.: Effect of reconstituted basement membrane on growth and secretory function in pancreatic acinar AR42J cells. Gastroenterol Jpn 1993;28:393–400.