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 secretagogues 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 microM 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.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: H Y
authors.initials: HY
authors.lastname: Gaisano
authors.forename: L J
authors.initials: LJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011493:Protein Kinase C / Q000819:agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology* / Q000031:analogs & derivatives; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D010446:Peptide Fragments; C067408:cholecystokinin (26-32), Tyr-Gly-Nle(28,31) phenethyl ester-; D002766:Cholecystokinin; D011493:Protein Kinase C; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium