Role of cAMP-dependent protein kinase in the regulation of platelet procoagulant activity.
The membrane microparticle (MP) formation and phosphatidylserine (PS) exposure evoked by platelet activation provide catalytic surfaces for thrombin generation. Several reports have indicated the effects of cAMP-elevating agents on agonist-induced MP formation and PS exposure; however, the mechanism still remains unclear. Here we show that inhibition of basal cyclic AMP-dependent protein kinase (PKA) activity incurred platelet MP formation and PS exposure. Pretreatment of platelets with cAMP-elevating agent, forskolin, abolished thrombin plus collagen-induced MP formation and PS exposure, and obviously decreased calcium ionophore-evoked MP shedding. Moreover, the inhibitory effects of forskolin on agonists-induced MP formation and PS exposure were reversed by the PKA inhibitor H89. PKA inhibitor-induced MP formation was dose-dependently inhibited by calpain inhibitor MDL28170, and forskolin abrogated thrombin plus collagen-induced calpain activation. In conclusion, PKA plays key roles in the regulation of platelet MP formation and PS exposure. PKA-mediated MP shedding is dependent on calpain activation.
Yan
Rong
R
Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, 37 Xueyuan Road, Haidian District, Beijing, China.
Wang
Zhicheng
Z
Yuan
Yanhong
Y
Cheng
Hong
H
Dai
Kesheng
K
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002154:Calpain / Q000494:pharmacology; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D010718:Phosphatidylserines; D047428:Protein Kinase Inhibitors; D005576:Colforsin; D000001:Calcimycin; D003094:Collagen; D017868:Cyclic AMP-Dependent Protein Kinases; D013917:Thrombin; D002154:Calpain