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Effects of Arachidonic Acid on Dopamine Synthesis, Spontaneous Release, and Uptake in Striatal Synaptosomes from the Rat
Author(s) -
L'hirondel M.,
Chéramy A.,
Godeheu G.,
Glowinski J.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64031406.x
Subject(s) - nomifensine , chemistry , arachidonic acid , synaptosome , dopamine , protein kinase c , endocrinology , medicine , biochemistry , biology , enzyme , in vitro , dopaminergic
Arachidonic acid (AA) markedly stimulated, in a dose‐dependent manner, the spontaneous release of [ 3 H]dopamine ([ 3 H]DA) continuously synthesized from [ 3 H]tyrosine in purified synaptosomes from the rat striatum. As estimated by simultaneous measurement of the rate of [ 3 H]H 2 O formation (an index of [ 3 H]tyrosine conversion into [ 3 H]DOPA), the AA response was associated with a progressive and dose‐dependent reduction of [ 3 H]DA synthesis. In contrast to AA, arachidic acid, oleic acid, and the methyl ester of AA (all at 10 −4 M ) did not modify [ 3 H]DA release. The AA (3 × 10 −5 M )‐evoked release of [ 3 H]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 [ 3 H]DA uptake into synaptosomes, with a complete blockade observed at 10 −4 M . However, AA (10 −4 M ) still stimulated [ 3 H]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 [ 3 H]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).