Skip to main content
SpringerLink
Log in

On the secretagogue effect of dibutyryl cyclic AMP in the rat exocrine pancreas

  • Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Summary

DbcAMP≥0.1 mM induces the discharge of exportable enzymes from rat pancreas fragments incubated in vitro. This effect is qualitatively similar to the action of physiological secretagogues acting via hormone receptors: 1) it is accompanied by the appearance of exocytotic images at the acinar cell apex; 2) it is energy dependent but energy supply is low while that required for the carbamylcholine or caerulein response is high and can only be afforded by oxidative phosphorylation; 3) it is calcium dependent, but no alteration of inward or outward calcium movement can be observed; 4) it is altered by agents known to disrupt the microfilamentous microtubular system [41]. However, the secretory response to DbcAMP is quantitatively less than that obtained with hormonal stimuli. A damaging effect of DbcAMP on pancreatic acinar cells is ruled out on histological and biochemical grounds: there is no significant leakage of LDH; protein synthesis, 2-deoxy-d-glucose andl-leucine uptake are unaltered. The secretagogue effect of DbcAMP is reversible, dose-related and specific. It is not mediated by neuro-transmitter release or by interaction with their receptors. The evidence presented points to a direct interaction of DbcAMP on the pancreatic acinar cell and suggests the last step of the secretory cycle as the most probable site of action of the nucleotide derivative.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

cAMP:

Adenosine-3′,5′-monophosphate

cyclic:

DbcAMP: N6-2′-O-Dibutyryl-adenosine-3′,5′-monophosphate, cyclic

DbcGMP:

N2-2′-O-Dibutyryl-guanosine-3′,5′-monophosphate, cyclic

5′-AMP:

Adenosine-5′-monophosphate

TCA:

Trichloracetic acid

ATP:

Adenosine triphosphate

NADH:

Nicotinamide-adenine dinucleotide

Tris:

Tris-(hydroxy-methyl) amino-methane

EGTA:

Ethylene glycol-bis (β aminoethylether)-NN′-tetraacetic acid

LDH:

Lactic dehydrogenase

References

  1. Bauduin, H., Colin, M., Dumont, J. E.: Energy sources for protein synthesis and enzymatic secretion in rat pancreas in vitro. Biochim. Biophys. Acta174, 722–733 (1969)

    Google Scholar 

  2. Bauduin, H., Rochus, L., Vincent, D., Dumont, J. E.: Role of cyclic 3′,5′-AMP in the action of physiological secretagogues on the metabolism of rat pancreas in vitro. Biochim. Biophys. Acta252, 171–183 (1971)

    Google Scholar 

  3. Bauduin, H., Stock, C., Vincent, D., Grenier, J. F.: Microfilamentous system and secretion of enzyme in the exocrine pancreas. Effect of cytochalasin B. J. Cell Biol.66, 165–181 (1975)

    Google Scholar 

  4. Benz, L., Eckstein, B., Matthews, E. K., Williams, J. A.: Control of pancreatic amylase release in vitro: effects of ions, cyclic AMP and colchicine. Br. J. Pharmacol.46, 66–77 (1972)

    Google Scholar 

  5. Berridge, M. J.: The interaction of cyclic nucleotides and calcium in the control of cellular activity. Adv. Cyclic Nucleotide Res.6, 1–98 (1976)

    Google Scholar 

  6. Case, R. M., Scratcherd, T.: The actions of dibutyryl cyclic adenosine 3′,5′-monophosphate and methylxanthines on pancreatic exocrine secretion. J. Physiol. (Lond.)223, 649–667 (1972)

    Google Scholar 

  7. Case, R. M., Johnson, M., Scratcherd, T., Sherratt, H. S. A.: Cyclic adenosine 3′,5′-monophosphate concentration in the pancreas following stimulation by secretin, cholecystokinin-pancreozymin and acetylcholine. J. Physiol. (Lond.)223, 669–684 (1972)

    Google Scholar 

  8. Case, R. M., Clausen, T.: The relationship between calcium exchange and enzyme secretion in the isolated rat pancreas. J. Physiol. (Lond.)235, 75–102 (1973)

    Google Scholar 

  9. Cenatiempo, Y., Mangeat, P., Marchis-Mouren, G.: Purification and properties of cyclic AMP dependent and independent protein kinases from rat pancreas. Biochimie57, 865–873 (1975)

    Google Scholar 

  10. Danielsson, A.: Technique for measuring amylase secretion from pieces of mouse pancreas. Anal. Biochem.59, 220–234 (1974)

    Google Scholar 

  11. Deschodt-Lanckman, M., Robberecht, P., De Neef, P., Labrie, F., Christophe, J.: In vitro interactions of gastrointestinal hormones on cyclic adenosine 3′,5′-monophosphate levels and amylase output in the rat pancreas. Gastroent.68, 318–325 (1975)

    Google Scholar 

  12. Fukuta, Y., Iwatsuki, K., Takeuchi, O., Hashimoto, K.: Secretin-like activity of dopamine on canine pancreatic secretion. Tohoku J. Exp. Med.108, 353–360 (1972)

    Google Scholar 

  13. Gardner, J. D., Conlon, T. P., Adams, T. D.: Cyclic AMP in pancreatic acinar cells. Effects of gastrointestinal hormones. Gastroent.70, 29–35 (1976)

    Google Scholar 

  14. Gillespie, E.: Microtubules, cyclic AMP, calcium and secretion. Ann. New York Acad. Sci.253, 771–779 (1975)

    Google Scholar 

  15. Haymovits, A., Scheele, G. A.: Cellular cyclic nucleotides and enzyme secretion in the pancreatic acinar cell. Proc. Natl. Acad. Sci. U.S.A.73, 156–160 (1976)

    Google Scholar 

  16. Heisler, S., Fast, D., Tenenhouse, A.: Role of Ca2+ and cyclic AMP in protein secretion from rat exocrine pancreas. Biochim. Biophys. Acta279, 561–572 (1972)

    Google Scholar 

  17. Heisler, S.: Calcium efflux and secretion of α-amylase from rat pancreas. Br. J. Pharmacol.52, 387–392 (1974)

    Google Scholar 

  18. Hilz, H., Tarnowski, W.: Opposite effects of cyclic AMP and its dibutyryl derivative on glycogen levels in Hela cells. Biochem. Biophys. Res. Commun.40, 973–981 (1970)

    Google Scholar 

  19. Hokin, L. E.: Effects of calcium omission on acetylcholine-stimulated amylase secretion and phospholipid synthesis in pigeon pancreas slices. Biochim. Biophys. Acta115, 219–221 (1966)

    Google Scholar 

  20. Jamieson, J. D., Palade, G. E.: Intracellular transport of secretory proteins in the pancreatic exocrine cell. IV. Metabolic requirements. J. Cell Biol.39, 589–603 (1968)

    Google Scholar 

  21. Jamieson, J. D., Palade, G. E.: Condensing vacuole conversion and zymogen granule discharge in pancreatic exocrine cells. Metabolic studies. J. Cell Biol.48, 503–522 (1971)

    Google Scholar 

  22. Jamieson, J. D., Palade, G. E.: Synthesis, intracellular transport and discharge of secretory proteins in stimulated pancreatic exocrine cells. J. Cell Biol.50, 135–158 (1971)

    Google Scholar 

  23. Kanno, T.: Calcium-dependent amylase release and electrophysiological measurements in cells of the pancreas. J. Physiol. (Lond.)226, 353–371 (1972)

    Google Scholar 

  24. Kempen, H. J. M., De Pont, J. J. H. H. M., Bonting, J. L.: Rat pancreas adenylate cyclase. II. Inactivation and protection of its hormone receptor sites. Biochim. Biophys. Acta370, 573–584 (1974)

    Google Scholar 

  25. Kempen, H. J. M.: Role of cyclic AMP in exocrine pancreatic secretion. Thesis. Nijmegen, Netherlands 1976

  26. Kondo, S., Schulz, I.: Calcium ion uptake in isolated pancreas cells induced by secretagogues. Biochim. Biophys. Acta419, 76–92 (1976)

    Google Scholar 

  27. Kulka, R. G., Sternlicht, E.: Enzyme secretion in mouse pancreas mediated by adenosine 3′,5′-cyclic phosphate and inhibited by adenosine 3′-phosphate. Proc. Natl. Acad. Sci. U.S.A.61, 1123–1128 (1968)

    Google Scholar 

  28. Marchis-Mouren, G., Sarda, L., Desnuelle, P.: Purification of hog pancreatic lipase. Arch. Biochem. Biophys.83, 309–319 (1959)

    Google Scholar 

  29. Morisset, J. A., Webster, P. D.: In vitro and in vivo effects of pancreozymin, urecholine and cyclic AMP on rat pancreas. Am. J. Physiol.230, 202–208 (1971)

    Google Scholar 

  30. Pederson, R., Schulz, I.: The effect of isoproterenol on enzyme secretion from the isolated perfused cat pancreas. Biochim. Biophys. Acta338, 440–446 (1974)

    Google Scholar 

  31. Petersen, O. H., Ueda, N.: Pancreatic acinar cells: the role of calcium in stimulus-secretion coupling. J. Physiol. (Lond.)254, 583–606 (1976)

    Google Scholar 

  32. Reboud, J. P., Ben Abdeljlil, A., Desnuelle, P.: Variations de la teneur en enzymes du pancréas de rat en fonction de la composition des régimes. Biochim. Biophys. Acta.58, 326–337 (1962)

    Google Scholar 

  33. Ridderstapp, A. S., Bonting, S. L.: Cyclic AMP and enzyme secretion by the isolated rabbit pancreas. Pflügers Arch.313, 62–70 (1969)

    Google Scholar 

  34. Rutten, W. J., De Pont, J. J. H. H. M., Bonting, S. L.: Adenylate cyclase in the rat pancreas; properties and stimulation by hormones. Biochim. Biophys. Acta274, 201–213 (1972)

    Google Scholar 

  35. Rutten, W. J., Schoot, B. M., De Pont, J. J. H. H. M., Bonting, S. L.: Adenosine 3′,5′-monophosphate phosphodiesterase in rat pancreas. Biochim. Biophys. Acta315, 384–393 (1973)

    Google Scholar 

  36. Schreurs, V. V. A. M., Swarts, H. G. P., De Pont, J. J. H. H. M., Bonting, S. L.: Role of calcium in exocrine pancreatic secretion. II. Comparison of the effects of carbachol and the ionophore A-23 187 on enzyme secretion and calcium movements in rabbit pancreas. Biochim. Biophys. Acta419, 320–330 (1976)

    Google Scholar 

  37. Schulz, I.: The role of extracellular Ca2+ and cyclic nucleotides in the mechanism of enzyme secretion from the cat pancreas. Pflügers Arch.360, 165–181 (1975)

    Google Scholar 

  38. Singh, M., Webster, P. O.: Effect of hormones on pancreatic macromolecular transport. Gastroent.68, 1536–1542 (1975)

    Google Scholar 

  39. Solomon, S. S., Brush, J. S., Kitabchi, A. E.: Divergent biological effects of adenosine and dibutyryl adenosine 3′,5′-monophosphate on the isolated fat cell. Science169, 387–388 (1970)

    Google Scholar 

  40. Stock, C., Vincent, D., Bauduin, H.: A propos de l'action sécrétagogue du dérivé dibutyrylé de l'adénosine monophosphate cyclique sur le pancréas exocrine du rat. Arch. Int. Physiol. Biochim.84, 348–350 (1976)

    Google Scholar 

  41. Stock, C., Launay, J. F., Grenier, J. F., Bauduin, H.: Vinblastine potentiates the secretagogue action of dibutyryl cyclic AMP on the exocrine pancreas. Biochem. Biophys. Res. Commun.76, 217–223 (1977)

    Google Scholar 

  42. Williams, J. A., Lee, M.: Pancreatic acinar cells: use of a Ca2+ ionophore to separate enzyme release from the earlier steps in stimulus-secretion coupling. Biochem. Biophys. Res. Commun.60, 542–548 (1974)

    Google Scholar 

  43. Williams, J. A., Lee, M.: Microtubules and pancreatic amylase release by mouse pancreas in vitro. J. Cell Biol.71, 795–806 (1976)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Medicine, Free University of Brussels, Laboratory of Biochemical Pharmacology, B-1000, Brussels, Belgium

    H. Bauduin & D. Vincent

  2. Unité de Recherches 61 de l'INSERM de Biophysiopathologie de l'Intestin, F-67200, Strasbourg, France

    C. Stock, J. F. Launay & J. F. Grenier

  3. Laboratory of Anatomical Pathology and Fondation Reine Elisabeth, Vrije Universiteit, B-1000, Brussels, Belgium

    P. Potvliege

Authors
  1. H. Bauduin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Stock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. F. Launay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Potvliege
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. F. Grenier
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was partially carried out under contracts from the Ministère de la Politique Scientifique within the framework of the Association Euratom—University of Brussels—University of Pisa, and the Institut National de la Santé et de la Recherche Médicale (France)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bauduin, H., Stock, C., Launay, J.F. et al. On the secretagogue effect of dibutyryl cyclic AMP in the rat exocrine pancreas. Pflugers Arch. 372, 69–76 (1977). https://doi.org/10.1007/BF00582208

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00582208

Key words

Search

Navigation