Modulation of protein kinase C translocation by excitatory and inhibitory amino acids in primary cultures of neurons.
In primary cultures of neurons from rat cerebral cortex and neostriatum, excitatory amino acids stimulate the translocation of protein kinase C (PKC) from the cytoplasm to the membrane. In the presence of a physiological concentration of Mg2+ in the extracellular medium, glutamate induces PKC translocation by binding to both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) excitatory amino acid receptors. Quisqualate translocates the enzyme by stimulating primarily AMPA receptors and possibly metabotropic receptors. NMDA receptor-induced PKC translocation is sodium independent, whereas quisqualate receptor-induced PKC translocation is sodium dependent; none of the agonists is active in the absence of calcium from the extracellular medium. Muscimol does not modify excitatory amino acid stimulation; however, blockade of gamma-aminobutyric acid(A) receptors by bicuculline greatly enhances glutamate-induced PKC translocation. This enhancement is blocked by the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) and by tetrodotoxin.
Vaccarino
F M
FM
Department of Psychiatry, Yale University, New Haven, Connecticut.
Liljequist
S
S
Tallman
J F
JF
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D007700:Kinetics; D009474:Neurons / Q000201:enzymology*; D010069:Oxadiazoles / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D000596:Amino Acids; D005971:Glutamates; D010069:Oxadiazoles; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015240:Phorbol 12,13-Dibutyrate; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D011493:Protein Kinase C; D001640:Bicuculline