title: Glycoprotein IIb/IIIa blockade inhibits platelet aminophospholipid exposure by potentiating translocase and attenuating scramblase activity.
abstract: The present study investigated the mechanisms underlying the inhibition of platelet phosphatidylserine (PS) exposure by GPIIb/IIIa blockade. Platelet PS exposure induced by thrombin stimulation was cell-cell contact dependent. GPIIb/IIIa blockade by c7E3 or SR121566 inhibited thrombin-induced platelet PS exposure. Thrombin stimulation induced mild, while A23187 induced extensive platelet-derived microparticle (PDMP) generation. Thrombin-induced PDMP generation was not inhibited by GPIIb/IIIa blockade. Aminophospholipid translocase activity was reduced upon platelet activation by thrombin. The reduction of non-PS-exposing platelets was attenuated by GPIIb/IIIa blockade, while little translocase activity was seen in PS-exposing platelets. Thrombin increased scramblase activity slightly in non-PS-exposing platelets, which was inhibited by GPIIb/IIIa blockade, and markedly enhanced scramblase activity in PS-exposing platelets. Activation of platelet calpain and caspase-3 or cytosolic calcium mobilization were not altered by GPIIb/IIIa inhibition. Thus, GPIIb/IIIa blockade inhibits platelet PS exposure by enhancing translocase activity and attenuating scramblase activity, but does not inhibit PDMP generation.
authors: Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: M
authors: M
authors: Razmara
authors: H
authors: H
authors: Hu
authors: M
authors: M
authors: Masquelier
authors: N
authors: N
authors: Li
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism
chemical_list: C493430:PLTP protein, human; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013917:Thrombin; D053148:Caspase 3; D002118:Calcium