Staurosporine potentiates platelet activating factor stimulated phospholipase C activity in rabbit platelets but does not block desensitization by platelet activating factor.
The possible involvement of protein kinase C activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets. PAF (100 nM for 5 seconds) stimulated incorporation of 32P into proteins and caused [3H]InsP3 levels to increase about 260% of control. These responses were compared after platelets were pretreated with either PAF, phorbol 12-myristate 13-acetate (PMA) or staurosporine and also after pretreatments with staurosporine followed by PAF or PMA. Pretreating platelets with staurosporine potentiated PAF-stimulated [3H]InsP3 levels by 54% and blocked protein phosphorylation. Pretreatments with PAF and PMA caused PAF-stimulated [3H]InsP3 levels to decrease to 115 and 136%, respectively. Staurosporine pretreatment blocked the decrease caused by the PMA pretreatment but not that by PAF. This study demonstrates that PAF-stimulated PLC activity is negatively affected by protein kinase C (PKC) activation and that inhibition of PKC activity did not prevent desensitization of PLC by PAF.
Department of Pharmacology, School of Medicine, University of Missouri-Columbia 65212.
W J
WJ
Morrison
A
A
Dhar
S D
SD
Shukla
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D004357:Drug Synergism; D066298:In Vitro Techniques; D007294:Inositol / Q000097:blood; D007295:Inositol Phosphates / Q000097:blood; D007700:Kinetics; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011817:Rabbits; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000097:blood*
D000470:Alkaloids; D007295:Inositol Phosphates; D010972:Platelet Activating Factor; D007294:Inositol; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate