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

Herbert Y. Gaisano, Laurence J Miller

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17 Citations (Scopus)

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

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Cholecystokinin
Protein Kinase C
Phosphorylation
Acinar Cells
Chemical activation
Cholecystokinin Receptors
Bombesin
Carbachol
Second Messenger Systems
Phorbol Esters
Esters
Acetates
Phosphotransferases
Temperature
Substrates
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "Complex role of protein kinase C in mediating the supramaximal inhibition of pancreatic secretion observed with cholecystokinin",
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.",
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AB - 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.

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