Studies on intracellular transport in the rat exocrine pancreas. I. Inhibition by aromatic amino acids in vitro.
In vitro incubation of rat pancreatic lobules in the presence of 10 mM concentrations of 2 natural (phenylalanine, tryptophane) and 2 modified aromatic amino acids (p-fluorophenylalanine, p-chlorophenylalanine) induces paracrystal formation in the cisternal space of the rough endoplasmic reticulum and in the acinar lumen. Aggregation of secretory material in transitional elements of the rough endoplasmic reticulum suggests tubular connection to the Golgi complex. Paracrystal formation is correlated with a disturbance of the three major phases in the secretory process of the exocrine cell. Incorporation of radioactive amino acids into proteins is inhibited by 10 mM concentrations of phenylalanine and tryptophane by 20 and 50% respectively and by p-chlorophenylalanine at 1 and 10 mM concentrations by 50 and 75%. The inhibition of protein synthesis is not due to a reduced intracellular concentration of radioactive precursor amino acids. Intracellular transport of newly synthesized proteins as studied by a radioassay for zymogen discharge and by cell fractionation is similarly inhibited by phenylalanine, tryptophane and p-chlorophenylalanine at 10 mM concentrarions (20, 30, and 40% respectively). Discharge of zymogens as measured by the secretion of amylase stimulated with 5 X 10(-6) M carbamylcholine is reduced by 20% if 10 mM concentrations of phenylalanine, tryptophane or p-chlorophenylalanine are present in the medium. Paracrystals were isolated by differential centrifugation and their protein content compared with isolated zymogen granules. On sodium dodecylsulfate gel electrophoresis paracrystalline proteins show the same electrophoretic pattern as the content of zymogen granules.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002250:Carbon Radioisotopes; D004721:Endoplasmic Reticulum; D006056:Golgi Apparatus; D008297:Male; D008854:Microscopy, Electron; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010649:Phenylalanine / Q000494:pharmacology; D051381:Rats; D014316:Tritium; D014364:Tryptophan / Q000494:pharmacology
D002250:Carbon Radioisotopes; D014316:Tritium; D010649:Phenylalanine; D014364:Tryptophan; D002217:Carbachol; D000681:Amylases