Protein kinase C isoform specificity of cholinergic potentiation of glucose-induced pulsatile 5-HT/ insulin release from mouse pancreatic islets.
Thymeleatoxin (TMX), an activator of Ca2+-sensitive protein kinase C (cPKC) isoforms, was used to assess the PKC isoform specificity of cholinergic potentiation of glucose (11 mM)-induced pulsatile 5-HT/insulin release (PIR) from single mouse pancreatic islets. TMX (100 nM) and carbachol (Cch, 50 microM) enhanced PIR approximately 3-fold while reducing the underlying [Ca2+]i oscillations (duration and amplitude) by approximately 40-50%. Both effects were ablated by the specific PKC inhibitor bisindolylmaleimide and chronic TMX pretreatment. Cch also evoked an initial transient [Ca2+]i rise and surge of 5-HT release, which remained unaffected by chronic TMX pretreatment. It is concluded that the immediate cholinergic responses are insensitive to cPKC. In contrast, specific activation of a cPKC isoform mediates sustained cholinergic potentiation of glucose-induced insulin secretion.
Baldeiras
Inês E
IE
Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
Santos
Rosa M
RM
Rosário
Luís M
LM
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004563:Electrochemistry; D005470:Fluorometry; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D011673:Pulsatile Flow / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*
D018679:Cholinergic Agonists; D007328:Insulin; D010703:Phorbol Esters; D012701:Serotonin; D002217:Carbachol; C080287:thymeleatoxin; D011493:Protein Kinase C; D005947:Glucose