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 CA1 and dentate regions of rat 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 not 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 CA1 and dentate regions of rat hippocampus and that the STP-enhancing effect of plasmin is independent of NMDA receptors.
Mizutani
A
A
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
Matsuki
N
N
D000818:Animals; D002401:Cathepsin B / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010450:Endopeptidases / Q000502:physiology*; D005341:Fibrinolysin / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010958:Plasminogen / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000502:physiology; D014357:Trypsin / Q000502:physiology
D015853:Cysteine Proteinase Inhibitors; D015842:Serine Proteinase Inhibitors; D010958:Plasminogen; D010450:Endopeptidases; D014357:Trypsin; D013917:Thrombin; D005341:Fibrinolysin; D002401:Cathepsin B