Direct and indirect presynaptic control of dopamine release by excitatory amino acids.
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. Glutamatergic 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 alpha-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 (10(-7) M), 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.
Chéramy
A
A
Chaire de Neuropharmacologie, INSERM U 114, Collège de France, Paris, France.
L'hirondel
M
M
Godeheu
G
G
Artaud
F
F
Glowinski
J
J
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D008274:Magnesium / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology*
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; D016718:Arachidonic Acid; D008274:Magnesium; D004298:Dopamine