trypsinogen and Hypertrophy

When pancreaticobiliary diversion (PBD) surgery was performed in rats, plasma CCK level increased, the pancreas grew mainly by proliferation, and pancreatic trypsinogen showed a remarkable increase, although amylase and lipase synthesis were somewhat decreased. The sensitivity of amylase release against CCK-8 in the pancreatic acini decreased when plasma CCK level was high. These changes in pancreatic growth and pancreatic enzyme secretion caused by PBD were completely inhibited by the CCK-receptor antagonist loxiglumide. From these results, intrinsic CCK was considered to play an important role in both pancreatic enzyme synthesis and proliferation.

Topics: Amylases; Animals; Biliary Tract Surgical Procedures; Cholecystokinin; Hypertrophy; Lipase; Male; Pancreas; Proglumide; Rats; Rats, Wistar; Secretin; Time Factors; Trypsinogen

Chronic diversion of pancreatic and biliary secretions away from the proximal small intestine resulted in rapid increases in pancreatic size and protein content in adult rats. The effect was detectable as early as 10 days postsurgery. Differential changes in pancreatic enzymes were evident after bypass. The concentration of trypsinogen remained stable while amylase concentrations showed a marked decrease. Total pancreatic trypsinogen content, however, was increased, while amylase content remained similar to controls. Feeding bypassed rats with chows containing various pancreatic and biliary supplements had no effect on the hyperplastic response of their pancreata. Trypsinogen and amylase levels in supplemented groups remained similar to the bypassed group fed nonsupplemented chow, with the exception of increases in trypsinogen concentration and content in the groups supplemented with bile and cotazyme plus bile acids. The adequacy of oral refeeding of pancreatic biliary components was supported by its effectiveness in restoring mucosal enterokinase activity and trypsin levels in segment 1. However, there was no correlation between tryptic activity in the contents of the bypassed segment and the eventual pancreatic weight. These results indicate that factors other than those supplemented in this study are required in maintaining the steady state of pancreatic growth in normal rats.

Topics: Ampulla of Vater; Animals; Bile; Bile Acids and Salts; Diet; Duodenum; Feedback; Hypertrophy; Jejunum; Lipase; Pancreas; Pancreatic Extracts; Pancreatic Juice; Pancrelipase; Rats; Rats, Inbred Strains; Trypsinogen

Topics: Amylases; Animals; DNA; Hyperplasia; Hypertrophy; Lipase; Male; Pancreas; Rats; Rats, Inbred Strains; Trypsin Inhibitors; Trypsinogen

The interrelationship between trypsin/trypsinogen and enterokinase (EK) was studied in rats following induction of trypsinogen hypersecretion by various agents. Both soybean trypsin inhibitor and para-aminobenzamidine increased intraluminal tryptic activities to a level about twice that found in the control rats. This resulted in an increase in the mucosal and the intraluminal contents of EK in the rat small intestine. On the other hand, in cholecystokinin-treated rats, although there was an increase of intraluminal trypsin, the increase was about 80% less than in the inhibitor-fed rats. Under this condition, there was no effect on the mucosal or the intraluminal EK. These results suggested that substantial increase in intraluminal trypsin/trypsinogen levels (two-fold over control) will increase the mucosal and the intraluminal concentrations of EK in the rat small intestine. Our observation extends previous reports that a decreased level of trypsin/trypsinogen, such as in pancreatic insufficiency, leads to a decrease in mucosal EK. These observations, when taken together, strongly support the modulating role of intraluminal trypsin/trypsinogen levels in controlling the EK concentrations in the small intestine.

Topics: 4-Aminobenzoic Acid; Animals; Cholecystokinin; Endopeptidases; Enteropeptidase; Enzyme Induction; Hypertrophy; Intestine, Small; Male; Pancreas; Rats; Rats, Inbred Strains; Time Factors; Trypsin Inhibitors; Trypsinogen; Weaning

Rats were given injections of caerulein, secretin, or a combination of these two peptides subcutaneously 3 times daily for 5, 10, or 15 days. Caerulein produced significant dose- and time-dependent increases in pancreatic weight and content of DNA, RNA, protein, amylase, and trypsinogen. Secretin produced significant increases in pancreatic weight and content of RNA and lipase after 15 days of treatment. After only 5 days of treatment with a combination of secretin plus caerulein, pancreatic weight and content of RNA and protein more than doubled, and trypsinogen content increased more than fivefold. Comparing the averages across the 5-, 10-, and 15-day values, increases in weight, protein, and trypsinogen with the combination of secretin plus caerulein were significantly greater than the sum of the effects of the peptides given singly. Using increase in DNA content as an index of hyperplasia and increases in the ratios of pancreatic weight, RNA content, and protein content to DNA content as indices of hypertrophy, we concluded that caerulein produced both hyperplasia and hypertrophy of rat pancreatic acinar cells. Secretin markedly augmented the hypertrophic action of caerulein but did not alter its hyperplastic action.

Topics: Amylases; Animals; Cell Division; Ceruletide; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hyperplasia; Hypertrophy; Lipase; Male; Pancreas; Rats; Secretin; Trypsinogen

Topics: Amylases; Animals; Cell Membrane; Chymotrypsin; Enzyme Precursors; Hypertrophy; Male; Nucleic Acids; Pancreas; Pancreatic Diseases; Proteins; Rats; Trypsin Inhibitors; Trypsinogen