Protein kinase C and platelet reactivity in spontaneously hypertensive rats.
Since protein kinase C (PKC) plays an important role in the control of platelet biological responses, we investigated whether it can be involved in the enhanced platelet reactivity to thrombin which is observed in spontaneously hypertensive rats (SHR) in comparison to that observed in controls (WKY). PKC activity was determined by measuring the phosphorylation of P47 protein (the endogenous substrate of PKC in the platelet). Mean effective concentration (EC50) values for phorbol ester and synthetic diacylglycerol (direct activators of PKC) were similar in SHR and WKY, thus revealing similar intrinsic activity of PKC in both rat strains. EC50 values for thrombin were approximately 30% lower in SHR v WKY. Enhanced PKC activity in SHR is likely the result of an increased diacylglycerol formation and release of Ca2+ from intracellular pools, consequent to an increased thrombin-induced phospholipase C activity.
Koutouzov
S
S
Department of Pharmacology, INSERM U7, CNRS UA318, Necker Hôpital, Paris, France.
Limon
I
I
Meyer
P
P
Marche
P
P
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D008297:Male; D010703:Phorbol Esters; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
D010703:Phorbol Esters; D012701:Serotonin; D011493:Protein Kinase C; D013917:Thrombin