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 via an institution to check access.
Similar content being viewed by others
References
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
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)
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)
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)
Gardner, J. D.: Regulation of pancreatic exocrine function in vitro: initial steps in the actions of secretagogues. Ann. Rev. Physiol.41, 55–66 (1979)
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)
Iwatsuki, N., Petersen, O. H.: Coupling and uncoupling of exocrine acinar cells. J. Cell Biol.79, 533–545 (1978b)
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)
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)
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)
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)
Author information
Authors and Affiliations
Rights 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
Issue Date:
DOI: https://doi.org/10.1007/BF00583711