Opposite presynaptic regulations by glutamate through NMDA receptors of dopamine synthesis and release in rat striatal synaptosomes |
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Authors: | Jean-Marie Desce, Ge rard Godeheu, Thierry Galli, Jacques Glowinski,Andre Che ramy |
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Affiliation: | aINSERM U 114, Colle`ge de France, Chaire de Neuropharmacologie, 11, Place Marcelin-Berthelot, 75231 Paris Cedex 05, France |
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Abstract: | Purified striatal synaptosomes were superfused continuously with L-[3,5-3H]tyrosine to measure simultaneously the synthesis ([3H]water formed during the conversion of [3H]tyrosine into [3H]DOPA) and the release of [3H]dopamine ([3H]DA). Glutamate (10−3 M) and NMDA (10−3 M, in the absence of Mg2+) stimulated the release of [3H]DA, but they reduced the efflux of [3H]water. This reduction of [3H]DA synthesis was blocked by 2-amino-5-phosphonovalerate indicating the involvement of NMDA receptors. Although D,L--amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) and kainate stimulated the release of [3H]DA, they did not affect its synthesis. The glutamate-evoked inhibition of [3H]DA synthesis was prevented when synaptosomes were superfused continuously with adenosine adenosine deaminase plus quinpirole, a treatment which markedly reduces the phosphorylation of tyrosine hydroxylase by cAMP dependent protein kinase. The opposite effects of glutamate on [3H]DA synthesis and release were mimicked by ionomycin (10−6 M). It is proposed that both an activation of a cyclic nucleotide phosphodiesterase and a dephosphorylation of tyrosine hydroxylase linked to the influx of calcium through NMDA receptors is responsible for the inhibition of dopamine synthesis by glutamate and that calcineurin could play a critical role in these processes. |
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Keywords: | Dopamine synthesis Dopamine release Synaptosome Striatum NMDA receptor |
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