The cholecystokinin receptor antagonist L-364,718 reduces taurocholate-induced pancreatitis in rats. 1996

K H Kim, and M G Lee, and D G Kim
Department of Pharmacology, Yonsei University, College of Medicine, Seoul, Korea. Hwan444@yumc.yonsei.ac.kr

CONCLUSIONS Our results suggest that the cholecystokinin (CCK) receptor antagonist L-364,718 has a protective effect on taurocholate-induced pancreatitis, and thus, it is inferred that CCK may have a significant pathophysiological role in the early phase of pancreatitis. BACKGROUND Conflicting results have been obtained from studies designed to determine the role of CCK in the initial stages of pancreatitis. METHODS We evaluated the protective effect of the CCK receptor antagonist L-364,718 (devazepide) and of the trypsin inhibitor camostat, on taurocholate-induced pancreatitis in rats. L-364,718 (1 mg/kg) or camostat (200 mg/kg) was administered intragastrically 30 min before the induction of pancreatitis. RESULTS Infusion of sodium taurocholate (50 mg/kg) into the pancreaticobiliary duct caused severe pancreatitis with marked hyperamylasemia and reduction of tissue enzyme content at 12 h postinfusion. Pretreatment with L-364,718, but not with camostat, caused significant improvement in signs of experimental pancreatitis based on tissue enzyme content and morphology. Compared with untreated pancreatitis, there was relatively well-preserved lobular architecture, less edema, less infiltration of inflammatory cells, and more zymogen granules after L-364,718 pretreatment. Moreover, the reduction of enzyme content owing to pancreatitis was ameliorated by L-364,718 pretreatment.

UI MeSH Term Description Entries
D008297 Male Males
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D010195 Pancreatitis INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis. Acute Edematous Pancreatitis,Acute Pancreatitis,Pancreatic Parenchyma with Edema,Pancreatic Parenchymal Edema,Pancreatitis, Acute,Pancreatitis, Acute Edematous,Peripancreatic Fat Necrosis,Acute Edematous Pancreatitides,Acute Pancreatitides,Edema, Pancreatic Parenchymal,Edematous Pancreatitides, Acute,Edematous Pancreatitis, Acute,Fat Necrosis, Peripancreatic,Necrosis, Peripancreatic Fat,Pancreatic Parenchymal Edemas,Pancreatitides, Acute,Pancreatitides, Acute Edematous,Parenchymal Edema, Pancreatic,Peripancreatic Fat Necroses
D011949 Receptors, Cholecystokinin Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood. CCK Receptors,Caerulein Receptors,Cholecystokinin Octapeptide Receptors,Cholecystokinin Receptors,Pancreozymin Receptors,Receptors, CCK,Receptors, Caerulein,Receptors, Pancreozymin,Receptors, Sincalide,Sincalide Receptors,CCK Receptor,CCK-4 Receptors,CCK-8 Receptors,Cholecystokinin Receptor,Receptors, CCK-4,Receptors, CCK-8,Receptors, Cholecystokinin Octapeptide,CCK 4 Receptors,CCK 8 Receptors,Octapeptide Receptors, Cholecystokinin,Receptor, CCK,Receptor, Cholecystokinin,Receptors, CCK 4,Receptors, CCK 8
D002756 Cholagogues and Choleretics Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic). Choleretics,Cholagogues,Cholagogues, Choleretics,Choleretics and Cholagogues,Hydrocholeretics
D004952 Esters Compounds derived from organic or inorganic acids in which at least one hydroxyl group is replaced by an –O-alkyl or another organic group. They can be represented by the structure formula RCOOR’ and are usually formed by the reaction between an acid and an alcohol with elimination of water. Ester
D006146 Guanidines A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.
D006651 Histocytochemistry Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods. Cytochemistry
D006727 Hormone Antagonists Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites. Antagonists, Hormone
D000681 Amylases A group of amylolytic enzymes that cleave starch, glycogen, and related alpha-1,4-glucans. (Stedman, 25th ed) EC 3.2.1.-. Diastase,Amylase

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