Depolarization and Neurotransmitters Increase Neuronal Protein Tyrosine Phosphorylation |
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Authors: | Julio C. Siciliano,Michè le Gelman,Jean-Antoine Girault |
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Affiliation: | INSERM U. 114, Chaire de Neuropharmacologie, Collège de France, Paris, France |
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Abstract: | Abstract: In rat hippocampal slices and in neurons in primary culture, K+-induced depolarization increased markedly and rapidly tyrosine phosphorylation of a 110-kDa protein (pp110) and, to a lesser degree, of a 120-kDa protein (pp120), in a calcium-dependent fashion. Qlutamate, 1-aminocyclopentane- trans -1,3-dicarboxylic acid (an agonist of metabotropic glutamate receptors), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (an agonist of ionotropic glutamate receptors) stimulated also tyrosine phosphorylation of pp110 and pp120. These effects were not observed in astrocytes in primary culture. In hippocampal slices tyrosine phosphorylation of pp110 and pp120 was stimulated by Ca2+-ionophores and by phorbol esters and antagonized by a chelator of intracellular Ca2+and by drugs that inhibit protein kinase C. Stimulation of muscarinic and α1,-adrenergic receptors increased also tyrosine phosphorylation of pp110 and pp120. These results demonstrate that membrane depolarization and stimulation of neurotransmitter receptors activate a tyrosine phosphorylation pathway in neurons. This pathway involves an increase in intracellular Ca2+ concentrations and the activation of protein kinase C. It may provide a biochemical basis for some neurotrophic effects of electrical activity and neurotransmitters and may contribute to the role of tyrosine phosphorylation in long-term potentiation. |
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Keywords: | Hippocampus Brain slices Cell culture Glutamate Norepinephrine Acetylcholine Calcium Protein kinase C |
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