The inhibitory effects of okadaic acid on platelet function.
Okadaic acid (OA), a potent inhibitor of protein phosphatases type 1 and type 2A, inhibited thrombin-induced platelet aggregation (IC50 = 0.8 microM), [14C]serotonin release and increase in intracellular Ca2+ ([Ca2+]i) in the same dose dependence. In the absence of thrombin OA increased the phosphorylation of 50-kDa protein and 20-kDa myosin light chain (MLC20). The 50-kDa protein phosphorylation was accomplished within a shorter time period and at a lower concentration than was the MLC20. OA decreased the thrombin-induced phosphorylation of 47-kDa protein and MLC20, although phosphorylation of MLC20 reincreased at higher concentrations of OA (5-10 microM). Since type 2A phosphatase is more sensitive to OA than type 1, these results suggest that type 2A phosphatases are involved in the regulation of Ca2+ signaling in thrombin-induced platelet activation.
Higashihara
M
M
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Takahata
K
K
Kurokawa
K
K
Ikebe
M
M
D001792:Blood Platelets / Q000378:metabolism; D004988:Ethers, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D019319:Okadaic Acid; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013917:Thrombin / Q000502:physiology*
D004988:Ethers, Cyclic; D010975:Platelet Aggregation Inhibitors; D019319:Okadaic Acid; D013917:Thrombin