Effects of Arachidonic Acid on Dopamine Synthesis, Spontaneous Release, and Uptake in Striatal Synaptosomes from the Rat

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Abstract
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, arachidic acid, oleic acid, and the methyl ester of AA (all at 10−4M) did not modify [3H]DA release. The AA (3 × 10−5M)-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 10−4M. However, AA (10−4M) 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 (10−4M)-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).

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