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. 1986 Nov;204(5):559–565. doi: 10.1097/00000658-198611000-00009

Evidence for dual modulation of pepsinogen secretion using isoproterenol, carbachol, CCK-8, forskolin, 8 bromo-cAMP, and A23187 probes.

G H Ballantyne, M J Zdon, D E Schafer, G R Fratesi, J R Roberts, M Tyshkov, I M Modlin
PMCID: PMC1251340  PMID: 3094467

Abstract

The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin-octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8-bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion.

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Selected References

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

  1. Amsterdam A., Jamieson J. D. Studies on dispersed pancreatic exocrine cells. I. Dissociation technique and morphologic characteristics of separated cells. J Cell Biol. 1974 Dec;63(3):1037–1056. doi: 10.1083/jcb.63.3.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berglindh T., Sachs G., Takeguchi N. Ca2+-dependent secretagogue stimulation in isolated rabbit gastric glands. Am J Physiol. 1980 Aug;239(2):G90–G94. doi: 10.1152/ajpgi.1980.239.2.G90. [DOI] [PubMed] [Google Scholar]
  3. Burnham D. B., Williams J. A. Activation of protein kinase activity in pancreatic acini by calcium and cAMP. Am J Physiol. 1984 May;246(5 Pt 1):G500–G508. doi: 10.1152/ajpgi.1984.246.5.G500. [DOI] [PubMed] [Google Scholar]
  4. Chew C. S. Forskolin stimulation of acid and pepsinogen secretion in isolated gastric glands. Am J Physiol. 1983 Nov;245(5 Pt 1):C371–C380. doi: 10.1152/ajpcell.1983.245.5.C371. [DOI] [PubMed] [Google Scholar]
  5. Chew C. S., Hersey S. J., Sachs G., Berglindh T. Histamine responsiveness of isolated gastric glands. Am J Physiol. 1980 Apr;238(4):G312–G320. doi: 10.1152/ajpgi.1980.238.4.G312. [DOI] [PubMed] [Google Scholar]
  6. Dockray G. J. Immunoreactive component resembling cholecystokinin octapeptide in intestine. Nature. 1977 Nov 24;270(5635):359–361. doi: 10.1038/270359a0. [DOI] [PubMed] [Google Scholar]
  7. Hersey S. J., May D., Schyberg D. Stimulation of pepsinogen release from isolated gastric glands by cholecystokininlike peptides. Am J Physiol. 1983 Feb;244(2):G192–G197. doi: 10.1152/ajpgi.1983.244.2.G192. [DOI] [PubMed] [Google Scholar]
  8. Hersey S. J., Miller M., May D., Norris S. H. Lack of interaction between acid and pepsinogen secretion in isolated gastric glands. Am J Physiol. 1983 Dec;245(6):G775–G779. doi: 10.1152/ajpgi.1983.245.6.G775. [DOI] [PubMed] [Google Scholar]
  9. Hersey S. J., Norris S. H., Gibert A. J. Cellular control of pepsinogen secretion. Annu Rev Physiol. 1984;46:393–402. doi: 10.1146/annurev.ph.46.030184.002141. [DOI] [PubMed] [Google Scholar]
  10. Johnson L. R. Regulation of pepsin secretion by topical acid in the stomach. Am J Physiol. 1972 Oct;223(4):847–850. doi: 10.1152/ajplegacy.1972.223.4.847. [DOI] [PubMed] [Google Scholar]
  11. Kasbekar D. K., Jensen R. T., Gardner J. D. Pepsinogen secretion from dispersed glands from rabbit stomach. Am J Physiol. 1983 Apr;244(4):G392–G396. doi: 10.1152/ajpgi.1983.244.4.G392. [DOI] [PubMed] [Google Scholar]
  12. Koelz H. R., Hersey S. J., Sachs G., Chew C. S. Pepsinogen release from isolated gastric glands. Am J Physiol. 1982 Sep;243(3):G218–G225. doi: 10.1152/ajpgi.1982.243.3.G218. [DOI] [PubMed] [Google Scholar]
  13. Muller J. E., Straus E., Yalow R. S. Cholecystokinin and its COOH-terminal octapeptide in the pig brain. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3035–3037. doi: 10.1073/pnas.74.7.3035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Raufman J. P., Kasbekar D. K., Jensen R. T., Gardner J. D. Potentiation of pepsinogen secretion from dispersed glands from rat stomach. Am J Physiol. 1983 Oct;245(4):G525–G530. doi: 10.1152/ajpgi.1983.245.4.G525. [DOI] [PubMed] [Google Scholar]
  15. Schulz I., Stolze H. H. The exocrine pancreas: the role of secretagogues, cyclic nucleotides, and calcium in enzyme secretion. Annu Rev Physiol. 1980;42:127–156. doi: 10.1146/annurev.ph.42.030180.001015. [DOI] [PubMed] [Google Scholar]
  16. Seamon K. B., Padgett W., Daly J. W. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3363–3367. doi: 10.1073/pnas.78.6.3363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sung C. P., Jenkins B. C., Burns L. R., Hackney V., Spenney J. G., Sachs G., Wiebelhaus V. D. Adenyl and guanyl cyclase in rabbit gastric mucosa. Am J Physiol. 1973 Dec;225(6):1359–1363. doi: 10.1152/ajplegacy.1973.225.6.1359. [DOI] [PubMed] [Google Scholar]
  18. Sutton D. R., Donaldson M., Jr Synthesis and secretion of protein and pepsinogen by rabbit gastric mucosa in organ culture. Gastroenterology. 1975 Jul;69(1):166–174. [PubMed] [Google Scholar]

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