Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

  • Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands
  • Published:

Separate activation sites for cholecystokinin and bombesin on pancreatic acini

An electrophysiological study employing a competitive antagonist for the action of CCK

  • 14 Accesses

  • 27 Citations

Abstract

The effects of dibutyryl cyclic guanosine 3′:5′ monophosphate (dbcGMP) on the electrical responses of in vitro mouse pancreatic acinar cells to caerulein, bombesin and acetylcholine, applied by microionophoresis, were investigated using intracellular microelectrode recordings. Exposure to dbcGMP (10−3 mol ·l−1) quickly abolished the depolarization response to caerulein ionophoresis, while the bombesin-nonapeptide and acetylcholine-induced depolarizations were retained.

Exposing acinar cells to 2×10−4 mol·l−1 dbcGMP reduced their sensitivity such that a 10-fold increase in the applied caerulein ionophoresis current was required to restore the responses to the same magnitude as those obtained in a dbcGMP-free environment. The response to topical applications of pentagastrin and CCK-33 were also abolished by dbcGMP.

The results provide direct evidence that functional ACh, bombesin and CCK receptors are all present within the same acinar cell unit. The dbcGMP-induced inhibition of responses evoked by CCK-like peptides is immediate, specific and easily reversible. DbcGMP acts as a competitive antagonist of the CCK receptor on pancreatic acinar cells.

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

References

  1. Christophe, J., Deschodt-Lanckman, M., Adler, M., Robberecht, P.: In vitro and in vivo effects of bombesin and bombesin-like peptides on the rat pancreas. Mechanism of action. In: First International Symposium on Hormonal Receptors in Digestive Tract Physiology (Bonfus et al. eds.), pp. 247–260. Amsterdam: Elsevier/North Holland Biomedical Press 1977

  2. Deschodt-Lanckman, M., Robberecht, P., De Neef, P., Lammens, M., Christophe, J.: In vitro action of bombesin and bombesin-like peptides on amylase secretion, calcium efflux and adenylate cyclase activity in the rat pancreas. J. Clin. Invest.58, 891–898 (1976)

  3. Dockray, G. J., Gregory, R. A., Hutchinson, J. B.: Isolation, structure and biological activity of two cholecystokinin octapeptides from sheep brain. Nature274, 711–713 (1978)

  4. Dodd, J., Kelly, J. S.: Excitation of CA1 pyramidal neurones of the hippocampus by the tetra- and octapeptide C-terminal fragments of cholecystokinin. Proc. Physiol. Soc. (Cambridge meeting) J. Physiol. (Lond.) (in press, 1979)

  5. Gardner, J. D.: Regulation of pancreatic exocrine function in vitro: initial steps in the actions of secretagogues. Ann. Rev. Physiol.41, 55–66 (1979)

  6. Iwatsuki, N., Petersen, O. H.: In vitro action of bombesin on amylase secretion, membrane potential and membrane resistance in rat and mouse pancreatic acinar cells. J. Clin. Invest.61, 41–46 (1978a)

  7. Iwatsuki, N., Petersen, O. H.: Coupling and uncoupling of exocrine acinar cells. J. Cell Biol.79, 533–545 (1978b)

  8. Peikin, S. R., Costenbader, C. L., Gardner, J. D.: Actions of derivatives of cyclic nucleotides on dispersed acini from guinea pig pancreas: discovery of a competitive antagonist of the action of cholecystokinin. J. Biol. Chem.254, 5321–5327 (1979)

  9. Petersen, O. H., Iwatsuki, N.: The role of calcium in pancreatic acinar cell stimulus secretion coupling: an electrophysiological approach. Ann. N. Y. Acad. Sci.307, 599–617 (1978)

  10. Petersen, O. H., Philpott, H. G.: Pancreatic acinar cells: effects of microionophoretic polypeptide application on membrane potential and resistance. J. Physiol. (Lond.)290, 305–315 (1979)

  11. Schulz, I., Stolze, H. H.: The exocrine pancreas: the role of secretagogues, cyclic nucleotides and calcium in enzyme secretion. Ann. Rev. Physiol. (in press, 1980)

Download references

Author information

Correspondence to O. H. Petersen.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Philpott, H.G., Petersen, O.H. Separate activation sites for cholecystokinin and bombesin on pancreatic acini. Pflugers Arch. 382, 263–267 (1979). https://doi.org/10.1007/BF00583711

Download citation

Key words

  • Pancreatic acinar cells
  • N2, O2′ dibutyryl guanosine 3′:5′-Monophosphate
  • Cholecystokinin antagonist
  • Bombesin
  • Membrane potential