Lipase synthesis in the rat pancreas is regulated by secretin.
Conscious rats were infused with optimal doses of secretin (16 clinical units [CU]/kg/h), cerulein (0.25 microgram/kg/h), and both for varying periods of time over 24 h. The presence of zymogen granules in acinar cells and the tissue content of enzymes showed progressive decreases over 3 and 12 h for cerulein and secretin stimulation, respectively. Stimulation with either hormone resulted in a two-fold increase in protein synthesis at 6 and 12 h. Kinetically, the increases observed in protein synthesis were not directly coupled to the observed decreases in tissue content of enzymes. Cerulein stimulation selectively increased the synthesis of anionic trypsinogen forms 1 and 2 and chymotrypsinogen forms 1 (anionic) and 2 (cationic) and decreased the synthesis of amylase. Secretin stimulation selectively promoted the synthesis of lipase and proelastase 2. Lipase synthesis was increased 2.8-, 5.8-, and 4.8-fold at 6, 12, and 24 h, respectively. Proelastase 2 synthesis was increased 2.3-, 3.0-, and 3.4-fold at the same time points. In combination, secretin and cerulein stimulation resulted largely in competitive effects, suggesting that the two hormones exert effects on protein synthesis through different mechanisms. The findings suggest that the anticoordinate changes observed in the synthesis of functional groups of pancreatic enzymes by nutritional substrates in the diet are modulated by specific hormones. Synthesis of the majority of protease zymogens but not cationic trypsinogen or proelastase 2 is modulated by cholecystokinin and its peptide analogs. In contrast, the synthesis of pancreatic lipase and proelastase 2 is regulated by secretin. The findings indicate for the first time that secretin regulates the synthesis of specific proteins in the exocrine pancreas.
D000818:Animals; D002108:Ceruletide / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000201:enzymology; D004792:Enzyme Precursors / Q000096:biosynthesis; D008049:Lipase / Q000096:biosynthesis*; D008297:Male; D010179:Pancreas / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012633:Secretin / Q000502:physiology*; D013268:Stimulation, Chemical
D004792:Enzyme Precursors; D012633:Secretin; D002108:Ceruletide; D008049:Lipase; C022443:proelastase; D010196:Pancreatic Elastase