Nitric Oxide Inhibits Thrombin Receptor-activating Peptide-induced Phosphoinositide 3-Kinase Activity in Human Platelets

摘要: Although nitric oxide (NO) has potent antiplatelet actions, the signaling pathways affected by NO in platelet are poorly understood. Since can induce disaggregation and phosphoinositide 3-kinase (PI3-kinase) activation renders aggregation irreversible, we tested hypothesis that exerts its effects at least part inhibiting PI3-kinase. The results demonstrate donor S-nitrosoglutathione (S-NO-glutathione) inhibits stimulation of PI3-kinase associated with tyrosine-phosphorylated proteins p85/PI3-kinase SRC family kinase member LYN following exposure platelets to thrombin receptor-activating peptide. LYN-associated was unrelated changes amount physically complexes but did require other tyrosine kinases. cyclic GMP-dependent activator 8-bromo-cyclic GMP had similar on activity, consistent a model which nucleotide mediates NO. Additional studies showed wortmannin S-NO-glutathione have additive inhibitory peptide-induced surface expression markers. These data provide evidence distinct novel mechanism for function.