Mannaioni, Guido Orr, Anna G. Hamill, Cecily E. Yuan, Hongjie Pedone, Katherine H. Mccoy, Kelly L. Palmini, Rolando Berlinguer Junge, Candice E. Lee, C. Justin Yepes, Manuel Hepler, John R. Traynelis, Stephen F. 2024-01-20T23:02:10Z 2024-01-20T23:02:10Z 2021-09-03 2008-07-18 0021-9258 https://pubs.kist.re.kr/handle/201004/133316 Protease-activated receptor-1 (PAR1) is activated by a number of serine proteases, including plasmin. Both PAR1 and plasminogen, the precursor of plasmin, are expressed in the central nervous system. In this study we examined the effects of plasmin in astrocyte and neuronal cultures as well as in hippocampal slices. We find that plasmin evokes an increase in both phosphoinositide hydrolysis (EC50 64 nM) and Fura-2/AM fluorescence (195 +/- 6.7% above base line, EC50 65 nM) in cortical cultured murine astrocytes. Plasmin also activates extracellular signal-regulated kinase (ERK1/2) within cultured astrocytes. The plasmin-induced rise in intracellular Ca2+ concentration ([Ca2+](i)) and the increase in phospho-ERK1/2 levels were diminished in PAR1(-/-) astrocytes and were blocked by 1 mu M BMS-200261, a selective PAR1 antagonist. However, plasmin had no detectable effect on ERK1/2 or [Ca2+](i) signaling in primary cultured hippocampal neurons or in CA1 pyramidal cells in hippocampal slices. Plasmin (100-200 nM) application potentiated the N-methyl-D-aspartate (NMDA) receptor-dependent component of miniature excitatory postsynaptic currents recorded from CA1 pyramidal neurons but had no effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate- or gamma-aminobutyric acid receptor-mediated synaptic currents. Plasmin also increased NMDA-induced whole cell receptor currents recorded from CA1 pyramidal cells (2.5 +/- 0.3-fold potentiation over control). This effect was blocked by BMS-200261 (1 mu M; 1.02 +/- 0.09-fold potentiation over control). These data suggest that plasmin may serve as an endogenous PAR1 activator that can increase [Ca2+](i) in astrocytes and potentiate NMDA receptor synaptic currents in CA1 pyramidal neurons. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC LONG-TERM POTENTIATION THROMBIN RECEPTOR LYSOPHOSPHATIDIC ACID MICE LACKING LATE-PHASE SYSTEM EXPRESSION GLUTAMATE CURRENTS LOCALIZATION Plasmin potentiates synaptic N-methyl-D-aspartate receptor function in hippocampal neurons through activation of protease-activated receptor-1 Article 10.1074/jbc.M803015200 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.283, no.29, pp.20600 - 20611 JOURNAL OF BIOLOGICAL CHEMISTRY 283 29 20600 20611 scie scopus 000257565300072 2-s2.0-50649100200 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article LONG-TERM POTENTIATION THROMBIN RECEPTOR LYSOPHOSPHATIDIC ACID MICE LACKING LATE-PHASE SYSTEM EXPRESSION GLUTAMATE CURRENTS LOCALIZATION NMDA receptor glycine d-serine