salicylates and chelerythrine

The N-methyl-D-aspartate (NMDA) receptor contributes to synaptic plasticity in the central nervous system and is both serine-threonine and tyrosine phosphorylated. In CA1 pyramidal neurons of the hippocampus, activators of protein kinase C (PKC) as well as the G-protein-coupled receptor ligands muscarine and lysophosphatidic acid enhanced NMDA-evoked currents. Unexpectedly, this effect was blocked by inhibitors of tyrosine kinases, including a Src required sequence and an antibody selective for Src itself. In neurons from mice lacking c-Src, PKC-dependent upregulation was absent. Thus, G-protein-coupled receptors can regulate NMDA receptor function indirectly through a PKC-dependent activation of the non-receptor tyrosine kinase (Src) signaling cascade.

Topics: Alkaloids; Amino Acid Sequence; Animals; Benzophenanthridines; Cells, Cultured; Enzyme Activation; Enzyme Inhibitors; Genistein; GTP-Binding Proteins; Isoflavones; Lysophospholipids; meta-Aminobenzoates; Mice; Mice, Knockout; Microinjections; Molecular Sequence Data; Muscarine; Nerve Tissue Proteins; Neuronal Plasticity; Oocytes; Patch-Clamp Techniques; Phenanthridines; Phenols; Phosphorylation; Protein Kinase C; Protein Processing, Post-Translational; Proto-Oncogene Proteins pp60(c-src); Pyramidal Cells; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Lysophosphatidic Acid; Receptors, Muscarinic; Receptors, N-Methyl-D-Aspartate; Salicylates; Signal Transduction; Tetradecanoylphorbol Acetate; Xenopus laevis