Possible involvement of plasmin in long-term potentiation of rat hippocampal slices

Effects of proteases and protease inhibitors on generation of long-term potentiation (LTP) were investigated in the CAI and dentate regions of rai hippocampus. Plasmin, a serine protease, and its precursor plasminogen significantly enhanced short-term potentiation (STP) induced by a weak tetanic stimulation, without affecting basal responses. The STP-enhancing effect of plasmin disappeared by concomitant perfusion of alpha(2)-antiplasmin, an endogenous plasmin inhibitor, Other proteases, such as thrombin, trypsin and cathepsin B, did not affect STP. On the other hand, alpha(2)-antiplasmin and leupeptin significantly attenuated LTP induced by a strong tetanus though plasminogen or plasmin itself did nor influence LTP. Furthermore, plasminogen and plasmin did not affect NMDA receptor-mediated synaptic responses in the absence of extracellular Mg2+. These results suggest that endogenous plasmin is:involved in the mechanism of LTP in CAL and dentate regions of rat hippocampus and that the STP-enhancing effect of plasmin is independent of NMDA receptors.