[Study on the mechanisms of thrombin to inhibit neurite outgrowth]

In the present study, we investigated the effects and signal transduction mechanisms of thrombin on neuronal differentiation of human primitive neuroectodermal tumor cell line CHP-100. Thrombin inhibited neurite outgrowth of CHP-100 cells in culture induced by serum removal. The inhibitory effects were found to be associated with activation of phosphatidylinositol turnover/calcium mobilization signal transduction pathway by thrombin, since stimulation with thrombin induced significant inositol-1, 4, 5 trisphosphate accumulation and intracellular free calcium transient in CHP-100 cells. In addition, the most potent inhibitor of thrombin hirudin, which reversed the inhibitory effect of thrombin on neurite outgrowth of CHP-100 cells, also inhibited thrombin-stimulated calcium transient. These results suggest a specific role of thrombin signal transduction pathway in the regulation of neuronal differentiation.