Thrombin-induced effects are selectively inhibited following treatment of intact human platelets with okadaic acid.
The involvement of protein phosphatases in regulating platelet activation was studied. The major portion of the phosphorylase phosphatase activity found in platelet lysates appears to be of the type 1 variety. The identification of this enzyme was based on the finding that greater than 80% of protein phosphatase activity was inhibited by the heat-stable inhibitor protein inhibitor 2 and, while only 20% of the phosphorylase phosphatase activity in platelet extracts was inhibited by 2 nM okadaic acid, greater than 95% of the activity was inhibited in the presence of 1 microM okadaic acid. Increases in protein phosphorylations occurred and thrombin-induced release of serotonin was prevented as a result of artificially inhibiting the enzyme with okadaic acid in intact platelets. This implies either that the regulation of okadaic acid sensitive protein phosphatases is necessary for some agonist-induced effects or that okadaic acid sensitive phosphatases are required for maintaining platelets in a responsive state.
Lerea
K M
KM
Department of Cell Biology and Anatomy, New York Medical College, Valhalla 10595.
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins; D004722:Endoribonucleases; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology*; D016601:RNA-Binding Proteins; D012694:Serine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000097847:Protein Phosphatase Inhibitory Proteins
D002352:Carrier Proteins; D004722:Endoribonucleases; D004988:Ethers, Cyclic; D047908:Intracellular Signaling Peptides and Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D011506:Proteins; D016601:RNA-Binding Proteins; D012694:Serine; D012701:Serotonin; D013912:Threonine; D013917:Thrombin; C021042:protein phosphatase inhibitor-1; C024833:protein phosphatase inhibitor-2; D000097847:Protein Phosphatase Inhibitory Proteins; C097081:PPP1R8 protein, human