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 [H-3]dopamine ([H-3]DA) continuously synth esized from [H-3]tyrosine in purified synaptosomes from the rat striat um. As estimated by simultaneous measurement of the rate of [H-3] H2O formation (an index of [H-3]tyrosine conversion into [H-3]DOPA), the A A response was associated with a progressive and dose-dependent reduct ion of [H-3]DA synthesis. In contrast to AA, arachidic acid, oleic aci d, and the methyl ester of AA (all at 10(-4) M) did not modify [H-3] D A release. The AA (3 x 10(-5) M)-evoked release of [H-3] DA was not af fected by inhibiting AA metabolism, with either 5,8,11,14-eicosatetray noic acid or metyrapone, suggesting that AA acts directly and not thro ugh one of its metabolites. AA also inhibited in a dose-dependent mann er [H-3] DA uptake into synaptosomes, with a complete blockade observe d at 10(-4) M. However, AA (10(-4) M) st ill stimulated [H-3] DA spont aneous release in the presence of either nomifensine or other DA uptak e inhibitors, indicating that AA both inhibits DA reuptake and facilit ates its release process. Finally, the AA(10(-4) M)-evoked release of [H-3] 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 (Re 31-7549 or chelerythrine).