Complex role of protein kinase C in mediating the supramaximal inhibition of pancreatic secretion observed with cholecystokinin

Herbert Y. Gaisano, Laurence J. Miller

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Protein kinase C appears to play an important, yet complex role in the supramaximal inhibition of pancreatic acinar cell secretion observed in response to cholecystokinin (CCK). The addition of protein kinase C activation to the concentration-response curve of a partial agonist acting at the CCK receptor (a phenethyl ester analogue of CCK), transforms a curve without supramaximal inhibition to a full agonist curve typical of CCK. This effect can be elicited by low concentrations of phorbol ester (50pM to 1nM 120-tetradecanoyl-phorbol-13-acetate) or by hormonal agonists (0.1μM carbamylcholine, 10pM bombesin, 1pM CCK-8) which activate protein kinase C, but not by agonists acting via alternate second messengers (VIP). Of interest, this effect is dependent on preincubation of the acinar cells with the protein kinase C activator at 37°C, with the effect rapidly reversed by transient exposure of the cells to lower temperature. This is consistent with mediation by a phosphorylation event. However, the requirement for an extended (>15 min) preincubation period when using minimal kinase activation suggests that this phenomenon is more complicated than a simple bimolecular phosphorylation event and likely includes a series of events such as translocation of substrates and/or enzymes involved.

Original languageEnglish (US)
Pages (from-to)498-506
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume187
Issue number1
DOIs
StatePublished - Aug 31 1992

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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