Dissociation between exocytosis and Ca(2+)-channel activity in mouse pancreatic beta-cells stimulated with calmidazolium (compound R24571).
Calmidazolium, a calmodulin inhibitor, suppressed influx of Ca2+ through voltage-gated Ca2+ channels in mouse pancreatic beta-cells. Despite this fact, calmidazolium stimulated insulin release from beta-cells at basal glucose concentration. This effect was not mediated by protein kinase C (PKC), since it persisted in PKC-depleted cells. RpcAMPS significantly attenuated the calmidazolium-stimulated insulin secretion, indicating that calmidazolium acts, at least partly, through PKA. The compound also stimulated insulin secretion from electropermeabilized beta-cells, indicating effects on distal steps in the stimulus-secretion coupling. The use of calmidazolium offers possibilities to investigate the mechanisms activating exocytosis under conditions where the cytoplasmic-free Ca2+ concentration does not increase.
Kindmark
H
H
Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Køohler
M
M
Larsson
O
O
Khan
A
A
Berggren
P O
PO
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D015640:Ion Channel Gating / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology
D015220:Calcium Channels; D002147:Calmodulin; D007093:Imidazoles; D007328:Insulin; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; C031938:calmidazolium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D005947:Glucose