Contribution of endogenously formed arachidonic acid in the presynaptic facilitatory effects of NMDA and carbachol on dopamine release in the mouse striatum.
Arachidonic acid stimulated the release of [3H]-dopamine from striatal microdiscs in a concentration-dependent and partially calcium-dependent manner. Inhibitors of cytosolic and membrane-bound phospholipase A2 were used to determine whether endogenously formed arachidonic acid also contributes to the release of [3H]-DA (previously taken up in tissues or endogenously synthesized from [3H]-tyrosine) evoked by N-methyl-d-aspartate (NMDA) and carbachol alone or in combination. In the presence of magnesium, carbachol was found to remove the magnesium block of NMDA receptors and to facilitate the NMDA-evoked release of [3H]-DA from striatal microdiscs and synaptosomes. In addition, in the absence of magnesium, synergistic responses were induced by both agonists on microdiscs but not on synaptosomes. Responses induced by NMDA, carbachol or both agonists on microdiscs were reduced by phospholipase A2 inhibitors, the most striking effects being observed with mepacrine. Mepacrine was also shown to reduce the oxotremorine, but neither the nicotine- nor the potassium-evoked release of [3H]-DA. Tetrodotoxin decreased the release of [3H]-DA evoked by the co-application of NMDA and carbachol on microdiscs, but mepacrine still decreased this tetrodotoxin-resistant response. Similarly, mepacrine still decreased the release of [3H]-DA evoked by NMDA and carbachol on synaptosomes. Altogether, these results indicate that arachidonic acid which is formed in striatal neurons, and to a lesser extent in DA fibres, under stimulation of NMDA and muscarinic receptors, partially contributes to the presynaptic facilitation of DA release evoked by NMDA and carbachol.
L'hirondel
M
M
INSERM U114, Collège de France, Paris.
Chéramy
A
A
Artaud
F
F
Godeheu
G
G
Glowinski
J
J
D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004351:Drug Resistance; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008274:Magnesium / Q000502:physiology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D017729:Presynaptic Terminals / Q000187:drug effects*; D011796:Quinacrine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D016718:Arachidonic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D002217:Carbachol; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D008274:Magnesium; D004298:Dopamine