Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1987 Feb 1;104(2):243–252. doi: 10.1083/jcb.104.2.243

Phasic release of newly synthesized secretory proteins in the unstimulated rat exocrine pancreas

PMCID: PMC2114415  PMID: 2433293

Abstract

Pancreatic lobules from fasted rats secrete pulse-labeled proteins in two phases comprising 15 and 85% of basal output, respectively. The first (0-6.5 h) is initially (less than or equal to 0.5 h) unstimulated by secretagogues, probably represents vesicular traffic of Golgi and post-Golgi origin (including condensing vaculoles/immature granules), and notably contains two groups of polypeptides with distinct release rates: zymogens (t1/2 approximately 2.4 h) and minor nonzymogens plus one unique zymogen (t1/2 approximately 1 h). The second phase (peak at 9-10 h) is stimulable, probably represents basal granule exocytosis (t1/2 approximately 5 h), and contains zymogens exclusively. Newly synthesized proteins released in both phases appear asynchronously, reiterating their asynchronous transport through intracellular compartments. Zymogens in both phases are secreted apically. The sorting of first from second phase zymogen release does not appear to be carrier-mediated, although the sorting of zymogens from other secretory proteins may use this process. Finally, data are presented that suggest that both secretory phases are subject to physiologic regulation.

Full Text

The Full Text of this article is available as a PDF (1.8 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bieger W., Seybold J., Kern H. F. Studies on intracellular transport of secretory proteins in the rat exocrine pancreas. V. Kinetic studies on accelerated transport following caerulein infusion in vivo. Cell Tissue Res. 1976 Jul 26;170(2):203–219. doi: 10.1007/BF00224299. [DOI] [PubMed] [Google Scholar]
  2. Burgess T. L., Craik C. S., Kelly R. B. The exocrine protein trypsinogen is targeted into the secretory granules of an endocrine cell line: studies by gene transfer. J Cell Biol. 1985 Aug;101(2):639–645. doi: 10.1083/jcb.101.2.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fries E., Gustafsson L., Peterson P. A. Four secretory proteins synthesized by hepatocytes are transported from endoplasmic reticulum to Golgi complex at different rates. EMBO J. 1984 Jan;3(1):147–152. doi: 10.1002/j.1460-2075.1984.tb01775.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gumbiner B., Kelly R. B. Two distinct intracellular pathways transport secretory and membrane glycoproteins to the surface of pituitary tumor cells. Cell. 1982 Jan;28(1):51–59. doi: 10.1016/0092-8674(82)90374-9. [DOI] [PubMed] [Google Scholar]
  5. Havinga J. R., Strous G. J., Poort C. Biosynthesis of the major glycoprotein associated with zymogen-granule membranes in the pancreas. Eur J Biochem. 1983 Jun 15;133(2):449–454. doi: 10.1111/j.1432-1033.1983.tb07484.x. [DOI] [PubMed] [Google Scholar]
  6. Herzog V., Farquhar M. G. Luminal membrane retrieved after exocytosis reaches most golgi cisternae in secretory cells. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5073–5077. doi: 10.1073/pnas.74.11.5073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Iacino D., Scheele G. A., Liebow C. Secretory response of the rabbit pancreas to cholecystokinin stimulation. Am J Physiol. 1980 Oct;239(4):G247–G254. doi: 10.1152/ajpgi.1980.239.4.G247. [DOI] [PubMed] [Google Scholar]
  8. Iwanij V., Jamieson J. D. Biochemical analysis of secretory proteins synthesized by normal rat pancreas and by pancreatic acinar tumor cells. J Cell Biol. 1982 Dec;95(3):734–741. doi: 10.1083/jcb.95.3.734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jamieson J. D., Palade G. E. Intracellular transport of secretory proteins in the pancreatic exocrine cell. II. Transport to condensing vacuoles and zymogen granules. J Cell Biol. 1967 Aug;34(2):597–615. doi: 10.1083/jcb.34.2.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jung D. H. Preparation and application of Procion Yellow starch for amylase assay. Clin Chim Acta. 1980 Jan 1;100(1):7–11. doi: 10.1016/0009-8981(80)90179-5. [DOI] [PubMed] [Google Scholar]
  11. Kelly R. B. Pathways of protein secretion in eukaryotes. Science. 1985 Oct 4;230(4721):25–32. doi: 10.1126/science.2994224. [DOI] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Lodish H. F., Kong N., Snider M., Strous G. J. Hepatoma secretory proteins migrate from rough endoplasmic reticulum to Golgi at characteristic rates. Nature. 1983 Jul 7;304(5921):80–83. doi: 10.1038/304080a0. [DOI] [PubMed] [Google Scholar]
  14. Moore H. H., Kelly R. B. Re-routing of a secretory protein by fusion with human growth hormone sequences. Nature. 1986 May 22;321(6068):443–446. doi: 10.1038/321443a0. [DOI] [PubMed] [Google Scholar]
  15. Moore H. P., Kelly R. B. Secretory protein targeting in a pituitary cell line: differential transport of foreign secretory proteins to distinct secretory pathways. J Cell Biol. 1985 Nov;101(5 Pt 1):1773–1781. doi: 10.1083/jcb.101.5.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Moore H. P., Walker M. D., Lee F., Kelly R. B. Expressing a human proinsulin cDNA in a mouse ACTH-secreting cell. Intracellular storage, proteolytic processing, and secretion on stimulation. Cell. 1983 Dec;35(2 Pt 1):531–538. doi: 10.1016/0092-8674(83)90187-3. [DOI] [PubMed] [Google Scholar]
  17. Palade G. Intracellular aspects of the process of protein synthesis. Science. 1975 Aug 1;189(4200):347–358. doi: 10.1126/science.1096303. [DOI] [PubMed] [Google Scholar]
  18. Rausch U., Vasiloudes P., Rüdiger K., Kern H. F. In-vivo stimulation of rat pancreatic acinar cells by infusion of secretin. II. Changes in individual rates of enzyme and isoenzyme biosynthesis. Cell Tissue Res. 1985;242(3):641–644. doi: 10.1007/BF00225431. [DOI] [PubMed] [Google Scholar]
  19. Robberecht P., Cremer M., Christophe J. Discharge of newly synthesized proteins in pure juice collected from the human pancreas. Indication of more than one pool of intracellular digestive enzymes. Gastroenterology. 1977 Mar;72(3):417–420. [PubMed] [Google Scholar]
  20. Roberge M., Beaudoin A. R. Newly synthesized secretory proteins from pig pancreas are not released from a homogeneous granule compartment. Biochim Biophys Acta. 1982 Jun 16;716(3):331–336. doi: 10.1016/0304-4165(82)90024-1. [DOI] [PubMed] [Google Scholar]
  21. Rothman S. S., Isenman L. D. Secretion of digestive enzyme derived from two parallel intracellular pools. Am J Physiol. 1974 May;226(5):1082–1087. doi: 10.1152/ajplegacy.1974.226.5.1082. [DOI] [PubMed] [Google Scholar]
  22. Salpeter M. M., Farquhar M. G. High resolution analysis of the secretory pathway in mammotrophs of the rat anterior pituitary. J Cell Biol. 1981 Oct;91(1):240–246. doi: 10.1083/jcb.91.1.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Scheele G. A., Palade G. E. Studies on the guinea pig pancreas. Parallel discharge of exocrine enzyme activities. J Biol Chem. 1975 Apr 10;250(7):2660–2670. [PubMed] [Google Scholar]
  24. Scheele G., Jacoby R., Carne T. Mechanism of compartmentation of secretory proteins: transport of exocrine pancreatic proteins across the microsomal membrane. J Cell Biol. 1980 Dec;87(3 Pt 1):611–628. doi: 10.1083/jcb.87.3.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scheele G., Tartakoff A. Exit of nonglycosylated secretory proteins from the rough endoplasmic reticulum is asynchronous in the exocrine pancreas. J Biol Chem. 1985 Jan 25;260(2):926–931. [PubMed] [Google Scholar]
  26. Schick J., Kern H., Scheele G. Hormonal stimulation in the exocrine pancreas results in coordinate and anticoordinate regulation of protein synthesis. J Cell Biol. 1984 Nov;99(5):1569–1574. doi: 10.1083/jcb.99.5.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schnaar R. L., Weigel P. H., Kuhlenschmidt M. S., Lee Y. C., Roseman S. Adhesion of chicken hepatocytes to polyacrylamide gels derivatized with N-acetylglucosamine. J Biol Chem. 1978 Nov 10;253(21):7940–7951. [PubMed] [Google Scholar]
  28. Sharoni Y., Eimerl S., Schramm M. Secretion of old versus new exportable protein in rat parotid slics. Control by neurotransmitters. J Cell Biol. 1976 Oct;71(1):107–122. doi: 10.1083/jcb.71.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Singh M. Nonparallel transport of exportable proteins in rat pancreas in vitro. Can J Physiol Pharmacol. 1982 May;60(5):597–603. doi: 10.1139/y82-080. [DOI] [PubMed] [Google Scholar]
  30. Tartakoff A., Vassalli P., Détraz M. Comparative studies of intracellular transport of secretory proteins. J Cell Biol. 1978 Dec;79(3):694–707. doi: 10.1083/jcb.79.3.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Uchiyama Y., Saito K. A morphometric study of 24-hour variations in subcellular structures of the rat pancreatic acinar cell. Cell Tissue Res. 1982;226(3):609–620. doi: 10.1007/BF00214788. [DOI] [PubMed] [Google Scholar]
  32. Udenfriend S., Stein S., Böhlen P., Dairman W., Leimgruber W., Weigele M. Fluorescamine: a reagent for assay of amino acids, peptides, proteins, and primary amines in the picomole range. Science. 1972 Nov 24;178(4063):871–872. doi: 10.1126/science.178.4063.871. [DOI] [PubMed] [Google Scholar]
  33. Van Nest G. A., MacDonald R. J., Raman R. K., Rutter W. J. Proteins synthesized and secreted during rat pancreatic development. J Cell Biol. 1980 Sep;86(3):784–794. doi: 10.1083/jcb.86.3.784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Vandermeers A., Khayat M. H., Rathé J., Christophe J. Vies moyennes de cinq hydrolases dans le pancréas du rat normal ou en malnutrition protidique. Biochim Biophys Acta. 1968 Jun 24;158(3):448–455. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES