Stimulation of pancreatic secretory process in the rat by low-molecular weight proteinase inhibitor. II. Regulation of total protein and individual enzyme biosynthesis.
Oral application of a single dose of a new synthetic proteinase inhibitor Camostate (Foy-305) in male Wistar rats was carried out together with studies of in vitro amino acid incorporation followed by separation of proteins by two-dimensional gel electrophoresis. The aim of this experiment was to analyze changes produced by the inhibitor in total protein and individual enzyme biosynthesis. Administration of 100 mg/kg Foy-305 resulted in significant inhibition of total pancreatic protein synthesis, without changes in fractional rates for individual enzymes. 50 mg/kg Foy-305 induced a 10-fold elevation of cholecystokinin (CCK) levels in serum; this persisted for 3 h and led to a significant increase in the total rate of protein synthesis with peak values at 6 and 9 h (78% and 84% above control levels, respectively), returning to control by 15 h. Changes in fractional rates of synthesis occurred with a latency of 6 h and were restricted to amylase and the anionic form of trypsinogen and chymotrypsinogen. Amylase biosynthesis decreased by about 40% from control levels at 9 h to return to control levels by 15 h. Increased synthesis of trypsinogen and chymotrypsinogen was observed; this was also phasic. The results show similar enzyme-specific regulation as previously described for exogenous CCK stimulation and for the adaptation of the pancreas to diets enriched in protein. They demonstrate the effectiveness of pulsatory endogenous hormone release in the regulation of protein synthesis.
D000681:Amylases / Q000096:biosynthesis; D000818:Animals; D002919:Chymotrypsinogen / Q000096:biosynthesis; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology*; D007700:Kinetics; D008049:Lipase / Q000096:biosynthesis; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011480:Protease Inhibitors / Q000494:pharmacology*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014362:Trypsinogen / Q000096:biosynthesis
D004952:Esters; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D016670:Gabexate; D014362:Trypsinogen; D002919:Chymotrypsinogen; D008049:Lipase; D000681:Amylases