Direct and indirect presynaptic control of dopamine release by excitatory amino acids |
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Authors: | Dr A Chéramy M L'hirondel G Godeheu F Artaud J Glowinski |
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Institution: | (1) Chaire de Neuropharmacologie, INSERM U 114, Collège de France 11 place Marcelin-Berthelot, F-75231 Paris 05, France |
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Abstract: | Summary Dopamine (DA) release from nerve terminals of the nigrostriatal DA neurons not only depends on the activity of nigral DA cells but also on presynaptic regulation. Glutamatergie neurons of cortical origin play a prominent role in these presynaptic regulations. The direct glutamatergic presynaptic control of DA release is mediated by N-methyl-D-aspartate (NMDA) and -amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) receptors, located on DA nerve terminals. In addition, by acting on striatal target cells, these glutamatergic neurons contribute also to indirect regulations of DA release involving several transmitters such as GABA, acetylcholine and neuropeptides. Diffusible messengers such as nitric oxide (NO) or arachidonic acid (AA) which are particularly formed under the stimulation of NMDA receptors may also participate to the regulation of DA release. In the present study, it will be shown that the co-application of NMDA and carbachol synergistically increases the release of 3H]-DA and that this effect is reduced by mepacrine or 4-bromophenacylbromide (107M), two inhibitors of PLA2. Therefore endogenously released AA induced by the co-stimulation of NMDA and cholinergic receptors seems to be involved, at least partly, in the release of DA. |
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Keywords: | Excitatory amino acids Dopamine release Mouse striatal microdiscs Presynaptic mechanisms Diffusible messengers Arachidonic acid |
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