Effects of arachidonic acid on dopamine synthesis, spontaneous release, and uptake in striatal synaptosomes from the rat.
Arachidonic acid (AA) markedly stimulated, in a dose-dependent manner, the spontaneous release of [3H]dopamine ([3H]DA) continuously synthesized from [3H]tyrosine in purified synaptosomes from the rat striatum. As estimated by simultaneous measurement of the rate of [3H]H2O formation (an index of [3H]tyrosine conversion into [3H]DOPA), the AA response was associated with a progressive and dose-dependent reduction of [3H]DA synthesis. In contrast to AA, arachidonic acid, oleic acid, and the methyl ester of AA (all at 10(-4) M) did not modify [3H]DA release. The AA (3 x 10(-5) M)-evoked release of [3H]DA was not affected by inhibiting AA metabolism, with either 5,8,11,14-eicosatetraynoic acid or metyrapone, suggesting that AA acts directly and not through one of its metabolites. AA also inhibited in a dose-dependent manner [3H]DA uptake into synaptosomes, with a complete blockade observed at 10(-4) M. However, AA (10(-4) M) still stimulated [3H]DA spontaneous release in the presence of either nomifensine or other DA uptake inhibitors, indicating that AA both inhibits DA reuptake and facilitates its release process. Finally, the AA (10(-4) M)-evoked release of [3H]DA was not affected by protein kinase A inhibitors (H-89 or Rp-8-Br-cAMPS) but was markedly reduced in the presence of protein kinase C inhibitors (Ro 31-7549 or chelerythrine).
L'hirondel
M
M
INSERM U114, Collège de France, Paris.
Chéramy
A
A
Godeheu
G
G
Glowinski
J
J
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001692:Biological Transport; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000378:metabolism
D016718:Arachidonic Acid; D011188:Potassium; D004298:Dopamine