title: Role of cAMP-dependent protein kinase in the regulation of platelet procoagulant activity.
abstract: 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.
authors.affiliation: Department of Biological Science and Technology, Beijing University of Aeronautics and Astronautics, 37 Xueyuan Road, Haidian District, Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yan
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Yuan
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.forename: Kesheng
authors.initials: K
authors.lastname: Dai
mesh_terms: 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
chemical_list: D010718:Phosphatidylserines; D047428:Protein Kinase Inhibitors; D005576:Colforsin; D000001:Calcimycin; D003094:Collagen; D017868:Cyclic AMP-Dependent Protein Kinases; D013917:Thrombin; D002154:Calpain