Low concentrations of protein kinase C-activating agonists suppress cholecystokinin-OPE-evoked Ca2+ mobilization in rat pancreatic acini

H. Y. Gaisano, Laurence J Miller

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The phenethyl ester analogues of cholecystokinin, OPE and JMV-180 are fully efficacious rat pancreatic secretagoguges which, unlike cholecystokinin (CCK), do not elicit supramaximal inhibition of secretion, and stimulate a sustained rise of cytosolic calcium ([Ca2+](i)) above basal levels. We have recently shown that low-level protein kinase C (PKC) activation by preincubation of acini with 1 nM 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or minimally secreting concentrations of PKC-activating receptor agonists (1 pM CCK-8, 0.1 μM carbachol or 10 pM bombesin) cause supramaximal inhibition of OPE-stimulated enzyme secretion. We now show that treatment of acini under these conditions also suppresses the sustained rise of [Ca2+](i) stimulated by OPE to basal levels in these cells, without changing the initial OPE- stimulated [Ca2+](i) peak. The resultant pattern of calcium signalling is similar to that evoked by supramaximal concentrations of native CCK. This suggests that even low concentrations of PKC activating agonists have the potential to induce inhibitory effects on Ca2+ mobilization and that this kinase is important in generating the supramaximal inhibition observed in response to CCK.

Original languageEnglish (US)
Pages (from-to)450-453
Number of pages4
JournalPancreas
Volume9
Issue number4
StatePublished - 1994

Fingerprint

Cholecystokinin
Protein Kinase C
Bombesin
Calcium Signaling
Carbachol
Tetradecanoylphorbol Acetate
Esters
Phosphotransferases
Calcium
Enzymes

Keywords

  • CA mobilization
  • Cholecystokinin
  • Heterologous agonists
  • OPE
  • Pancreatic acinar cell
  • Protein kinase C

ASJC Scopus subject areas

  • Endocrinology
  • Gastroenterology

Cite this

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title = "Low concentrations of protein kinase C-activating agonists suppress cholecystokinin-OPE-evoked Ca2+ mobilization in rat pancreatic acini",
abstract = "The phenethyl ester analogues of cholecystokinin, OPE and JMV-180 are fully efficacious rat pancreatic secretagoguges which, unlike cholecystokinin (CCK), do not elicit supramaximal inhibition of secretion, and stimulate a sustained rise of cytosolic calcium ([Ca2+](i)) above basal levels. We have recently shown that low-level protein kinase C (PKC) activation by preincubation of acini with 1 nM 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or minimally secreting concentrations of PKC-activating receptor agonists (1 pM CCK-8, 0.1 μM carbachol or 10 pM bombesin) cause supramaximal inhibition of OPE-stimulated enzyme secretion. We now show that treatment of acini under these conditions also suppresses the sustained rise of [Ca2+](i) stimulated by OPE to basal levels in these cells, without changing the initial OPE- stimulated [Ca2+](i) peak. The resultant pattern of calcium signalling is similar to that evoked by supramaximal concentrations of native CCK. This suggests that even low concentrations of PKC activating agonists have the potential to induce inhibitory effects on Ca2+ mobilization and that this kinase is important in generating the supramaximal inhibition observed in response to CCK.",
keywords = "CA mobilization, Cholecystokinin, Heterologous agonists, OPE, Pancreatic acinar cell, Protein kinase C",
author = "Gaisano, {H. Y.} and Miller, {Laurence J}",
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T1 - Low concentrations of protein kinase C-activating agonists suppress cholecystokinin-OPE-evoked Ca2+ mobilization in rat pancreatic acini

AU - Gaisano, H. Y.

AU - Miller, Laurence J

PY - 1994

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N2 - The phenethyl ester analogues of cholecystokinin, OPE and JMV-180 are fully efficacious rat pancreatic secretagoguges which, unlike cholecystokinin (CCK), do not elicit supramaximal inhibition of secretion, and stimulate a sustained rise of cytosolic calcium ([Ca2+](i)) above basal levels. We have recently shown that low-level protein kinase C (PKC) activation by preincubation of acini with 1 nM 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or minimally secreting concentrations of PKC-activating receptor agonists (1 pM CCK-8, 0.1 μM carbachol or 10 pM bombesin) cause supramaximal inhibition of OPE-stimulated enzyme secretion. We now show that treatment of acini under these conditions also suppresses the sustained rise of [Ca2+](i) stimulated by OPE to basal levels in these cells, without changing the initial OPE- stimulated [Ca2+](i) peak. The resultant pattern of calcium signalling is similar to that evoked by supramaximal concentrations of native CCK. This suggests that even low concentrations of PKC activating agonists have the potential to induce inhibitory effects on Ca2+ mobilization and that this kinase is important in generating the supramaximal inhibition observed in response to CCK.

AB - The phenethyl ester analogues of cholecystokinin, OPE and JMV-180 are fully efficacious rat pancreatic secretagoguges which, unlike cholecystokinin (CCK), do not elicit supramaximal inhibition of secretion, and stimulate a sustained rise of cytosolic calcium ([Ca2+](i)) above basal levels. We have recently shown that low-level protein kinase C (PKC) activation by preincubation of acini with 1 nM 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or minimally secreting concentrations of PKC-activating receptor agonists (1 pM CCK-8, 0.1 μM carbachol or 10 pM bombesin) cause supramaximal inhibition of OPE-stimulated enzyme secretion. We now show that treatment of acini under these conditions also suppresses the sustained rise of [Ca2+](i) stimulated by OPE to basal levels in these cells, without changing the initial OPE- stimulated [Ca2+](i) peak. The resultant pattern of calcium signalling is similar to that evoked by supramaximal concentrations of native CCK. This suggests that even low concentrations of PKC activating agonists have the potential to induce inhibitory effects on Ca2+ mobilization and that this kinase is important in generating the supramaximal inhibition observed in response to CCK.

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