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Platelet-derived Growth Factor Receptor-induced Feed-forward Inhibition of Excitatory Transmission between Hippocampal Pyramidal Neurons

Lei, Saobo ; Lu, Wei-Yang ; Xiong, Zhi-Gang ; Orser, Beverley Anne ; Valenzuela, Carlos Fernando ; MacDonald, John Ferguson

The Journal of biological chemistry, 1999-10, Vol.274 (43), p.30617-30623 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Platelet-derived Growth Factor Receptor-induced Feed-forward Inhibition of Excitatory Transmission between Hippocampal Pyramidal Neurons
Autor: Lei, Saobo ; Lu, Wei-Yang ; Xiong, Zhi-Gang ; Orser, Beverley Anne ; Valenzuela, Carlos Fernando ; MacDonald, John Ferguson
Assuntos: Animals ; Becaplermin ; Calcium - metabolism ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinases - pharmacology ; Enzyme Activation ; Enzyme Inhibitors - pharmacology ; Estrenes - pharmacology ; Evoked Potentials - drug effects ; Heparin - pharmacology ; Hippocampus - physiology ; Homeostasis ; In Vitro Techniques ; Isoenzymes - metabolism ; Mice ; N-Methylaspartate - pharmacology ; Patch-Clamp Techniques ; Peptide Fragments - pharmacology ; Phospholipase C gamma ; Platelet-Derived Growth Factor - pharmacology ; Protein-Tyrosine Kinases - metabolism ; Proto-Oncogene Proteins c-sis ; Pyramidal Cells - physiology ; Pyridines - pharmacology ; Pyrrolidinones - pharmacology ; Rats ; Rats, Wistar ; Receptors, Platelet-Derived Growth Factor - physiology ; Synaptic Transmission - drug effects ; Synaptic Transmission - physiology ; Type C Phospholipases - metabolism
É parte de: The Journal of biological chemistry, 1999-10, Vol.274 (43), p.30617-30623
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SourceType-Scholarly Journals-1
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Descrição: Growth factor receptors provide a major mechanism for the activation of the nonreceptor tyrosine kinase c-Src, and this kinase in turn up-regulates the activity ofN-methyl-d-aspartate (NMDA) receptors in CA1 hippocampal neurons (1). Unexpectedly, applications of platelet-derived growth factor (PDGF)-BB to cultured and isolated CA1 hippocampal neurons depressed NMDA-evoked currents. The PDGF-induced depression was blocked by a PDGF-selective tyrosine kinase inhibitor, by a selective inhibitor of phospholipase C-γ, and by blocking the intracellular release of Ca2+. Inhibitors of cAMP-dependent protein kinase (PKA) also eliminated the PDGF-induced depression, whereas a phosphodiesterase inhibitor enhanced it. The NMDA receptor-mediated component of excitatory synaptic currents was also inhibited by PDGF, and this inhibition was prevented by co-application of a PKA inhibitor. Src inhibitors also prevented this depression. In recordings from inside-out patches, the catalytic fragment of PKA did not itself alter NMDA single channel activity, but it blocked the up-regulation of these channels by a Src activator peptide. Thus, PDGF receptors depress NMDA channels through a Ca2+- and PKA-dependent inhibition of their modulation by c-Src.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Platelet-derived Growth Factor Receptor-induced Feed-forward Inhibition of Excitatory Transmission between Hippocampal Pyramidal Neurons

Lei, Saobo ; Lu, Wei-Yang ; Xiong, Zhi-Gang ; Orser, Beverley Anne ; Valenzuela, Carlos Fernando ; MacDonald, John Ferguson

United States: Elsevier Inc

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