Study on mechanism of newly found reverse signaling system in platelets

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Platelet-activating factor (PAF) is one of the most potent platelet agonists that promote platelet aggregation through its specific receptor. The binding of PAF to platelet receptors triggers intracellular responses such as activation of phospholipase C, D and AィイD22ィエD2 and many kinases and increases in cytosolic CaィイD12+ィエD1 concentration, which have been considered to occur transiently in association with platelet aggregation and serotonin secretion. The present study demonstrates that human and rabbit platelets fully aggregated by PAF were rapidly disaggregated by the PAF receptor antagonists. Accordingly, continuous binding of PAF to its receptor is considered to be necessary for prolonged platelet aggregation, which may be mediated through an unknown signaling system for a long-term cell response rather than a transient signaling system (Ref. 1). Most of PAF bound to platelets was metabolized extracellularly by ecto-type PAF acetylhydrolase. In order to clarify in more detail the binding behavior of PAF to its receptor, we investigated effects of intracellular signal transduction inhibitors such as many phosphatase inhibitors and kinase inhibitors on platelet disaggregation. The results suggested the presence of newly found reverse signaling system, which causes shape change and disaggregation of platelets. In addition, we found that extracellular CaィイD12+ィエD1 blocker nucleoside 5'-alkylphosphates (Ref. 5).