The effect of plasminogen on the intracellular Ca2+ concentration ([Ca]i) was examined in cultured rat hippocampal neurons. Plasminogen (100 nM) did not increase [Ca]i in the presence of tetrodotoxin (TTX, 3 μM) but increased [Ca]i in the absence of TTX. In all the cells which responded to plasminogen (100 nM), NMDA (5 μM) also increased [Ca]i in the presence of TTX. Furthermore, plasminogen (100 nM) enhanced the NMDA-evoked [Ca]i increase, and the potentiation by plasminogen was blocked by an NMDA receptor blocker, 2-amino-phosphonovalerate (APV). These data suggest that plasminogen enhances glutamate-evoked [Ca]i increase through modulation of NMDA receptor in hippocampal neurons.
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