Staurosporine inhibits protein kinases activated by Ca2+ and cyclic AMP in addition to inhibiting protein kinase C in rat islets of Langerhans.
Staurosporine has been used in several studies to investigate the role of protein kinase C (PKC) in secretory responses of islets of Langerhans to insulin secretagogues. We have assessed the effect of staurosporine on: [i] islet PKC activity in vitro; [ii] the stimulation of insulin secretion by nutrient secretagogues and [iii] the stimulation of protein phosphorylation and insulin secretion in electrically permeabilised islets. All experiments were carried out on rat isolated islets of Langerhans, either intact or permeabilised by high voltage discharge (3.4 kV/cm). The activity of PKC partially purified from rat islets was inhibited by staurosporine (1.6-400 nM) in a concentration-dependent manner. Staurosporine also inhibited insulin secretion stimulated by both glucose and glyceraldehyde, with maximal effects at 50 nM. After prolonged exposure of islets to the tumour-promoting phorbol ester, 4 beta phorbol myristate acetate (4 beta PMA), a procedure which depletes islet PKC activity, staurosporine still inhibited both glucose- and glyceraldehyde-stimulated insulin release. In electrically permeabilised islets, staurosporine inhibited both Ca(2+)- and cyclic AMP-stimulated protein phosphorylation and insulin secretion. These results suggest that staurosporine should not be used as a selective inhibitor of PKC in rat islets.
Biomedical Sciences Division, King's College London, UK.
S J
SJ
Persaud
P M
PM
Jones
S L
SL
Howell
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D007328:Insulin; D047428:Protein Kinase Inhibitors; D005985:Glyceraldehyde; D000242:Cyclic AMP; D011493:Protein Kinase C; D019311:Staurosporine; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium