CCK administration after CCK receptor blockade accelerates recovery from cerulein-induced acute pancreatitis in rats. 1998

S Nakano, and Y Kihara, and M Otsuki
Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

We examined the effects of treatment with cholecystokinin (CCK) octapeptide (CCK-8) and the CCK receptor antagonist loxiglumide on the recovery of exocrine pancreas in post-acute pancreatitic rats. Acute pancreatitis was induced in rats by intravenous infusion of 20 microg/kg/h cerulein for 4 h. At 24 h after the start of cerulein infusion, rats were divided into nine treatment groups: oral administration of saline (control), or oral administration of 10 or 50 mg/kg body weight loxiglumide twice daily for the first 3 days, followed by saline administration (Loxi-1 and Loxi-2), 10 or 50 mg/kg body weight loxiglumide twice daily for 6 days (Loxi-3 and Loxi-4), oral administration of saline or 10 or 50 mg/kg body weight loxiglumide twice daily for the first 3 days, followed by subcutaneous injection of 2.5 microg/kg body weight CCK-8 twice daily for the next 3 days (CCK-1, CCK-2, and CCK-3), and subcutaneous injection of 2.5 microg/kg body weight CCK-8 twice daily for 6 days (CCK-4). Pancreatic wet weight and biochemical changes were evaluated on day 8 at 12 h after the last treatment. Treatment with loxiglumide (Loxi-3 and Loxi-4) or CCK-8 for 6 days (CCK-4) or with a high dose of loxiglumide for the first 3 days (Loxi-2) significantly suppressed the recovery of pancreatic weight and DNA content compared to saline treatment or to the untreated normal control rats. However, when loxiglumide treatment was followed by 3 days of CCK-8 injections (CCK-2 and CCK-3), pancreatic protein and DNA content recovered to levels comparable to or above the control levels. The most remarkable increase in enzyme content was obtained in postpancreatitic rats treated with high-dose loxiglumide for the first 3 days, followed by CCK-8 injection (CCK-3). On the other hand, 6 days of CCK-8 treatment (CCK-4) had no significant influences on pancreatic enzyme contents. These results suggest that the most favorable strategy for the treatment of acute pancreatitis is to give high-dose loxiglumide during the early stage for only a short period, followed by CCK-8 administration.

UI MeSH Term Description Entries
D008049 Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. Triacylglycerol Lipase,Tributyrinase,Triglyceride Lipase,Acid Lipase,Acid Lipase A,Acid Lipase B,Acid Lipase I,Acid Lipase II,Exolipase,Monoester Lipase,Triacylglycerol Hydrolase,Triglyceridase,Triolean Hydrolase,Hydrolase, Triacylglycerol,Hydrolase, Triolean,Lipase A, Acid,Lipase B, Acid,Lipase I, Acid,Lipase II, Acid,Lipase, Acid,Lipase, Monoester,Lipase, Triglyceride
D008297 Male Males
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
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
D011377 Proglumide A drug that exerts an inhibitory effect on gastric secretion and reduces gastrointestinal motility. It is used clinically in the drug therapy of gastrointestinal ulcers. Xylamide,Milid,Xilamide
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
D012038 Regeneration The physiological renewal, repair, or replacement of tissue. Endogenous Regeneration,Regeneration, Endogenous,Regenerations
D002108 Ceruletide A specific decapeptide obtained from the skin of Hila caerulea, an Australian amphibian. Caerulein is similar in action and composition to CHOLECYSTOKININ. It stimulates gastric, biliary, and pancreatic secretion; and certain smooth muscle. It is used in paralytic ileus and as diagnostic aid in pancreatic malfunction. Caerulein,Cerulein,Ceruletid,FI-6934,Takus,FI 6934,FI6934
D002766 Cholecystokinin A peptide, of about 33 amino acids, secreted by the upper INTESTINAL MUCOSA and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. Pancreozymin,CCK-33,Cholecystokinin 33,Uropancreozymin

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