B. Lancaster et Mv. Rogers, A PEPTIDE ACTIVATOR OF ENDOGENOUS TYROSINE KINASE ENHANCES SYNAPTIC CURRENTS MEDIATED BY NMDA RECEPTORS, European journal of neuroscience, 10(7), 1998, pp. 2302-2308
N-methyl-D-aspartic acid (NMDA) receptor currents in cultured cells or
expression systems are increased by the addition of purified tyrosine
kinases. However, there is no direct demonstration of this effect at
NMDA receptors in intact synapses of rat brain slices. Transmitters wh
ich might be used to activate tyrosine kinases in situ are unlikely to
have a sufficiently selective action to allow a clear interpretation
of their effects. Therefore, we used a phosphotyrosine-containing deca
peptide which can be included in recording electrodes to activate post
synaptic src-family tyrosine kinases, This peptide enhanced NMDA respo
nses in dissociated hippocampal CA1 neurons. These effects were not re
produced by a non-phosphorylated peptide or a scrambled-sequence phosp
hopeptide. The enhancement of NMDA responses was blocked by a tyrosine
kinase inhibitor. In brain slices the phosphopeptide, but not control
peptide, increased NMDA receptor-mediated synaptic current indicating
that endogenous tyrosine kinase can upregulate the response of NMDA r
eceptors at glutamatergic synapses in the hippocampus.