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Facilitation of GABA release by arachidonic acid in rat hippocampal synaptosomes
Author(s) -
Cunha R. A.,
Ribeiro J. A.
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00661.x
Subject(s) - hippocampal formation , arachidonic acid , chelerythrine , endocrinology , inhibitory postsynaptic potential , medicine , phospholipase a2 , biology , chemistry , protein kinase c , biochemistry , enzyme
Arachidonic acid (AA) is proposed to be a facilitatory retrograde messenger in hippocampal glutamatergic synapses. In this study, we found that AA (10 μM) increased the basal outflow (19 ± 4%) and the K + ‐evoked release of [ 3 H]GABA (38 ± 3%) from rat hippocampal synaptosomes. This effect is likely to be a direct action of AA, as it was not mimicked by arachidic acid (10 μ M) and was not modified by inhibition of either lipooxygenase with nordihydroguaiaretic acid (50 μM) or cyclooxygenase with indomethacin (100 μM). Activation of protein kinase C may be involved, as chelerythrine (6 μM), a protein kinase C inhibitor, attenuated the AA (10 μM)‐facilitation of K + ‐evoked [ 3 H]GABA release by 58 ± 5%. Phospholipase A 2 (2 U/mL), an enzyme that releases AA, and melittin (1 μM), a phospholipase A 2 activator, mimicked the AA‐facilitation of evoked [ 3 H]GABA release (70 ± 6% and 76 ± 7% facilitation, respectively). These results show that exogenously added and endogenously produced AA increased basal outflow and K + ‐evoked release of [ 3 H]GABA from rat hippocampal synaptosomes. Thus, AA can no longer be considered solely a facilitatory neuromodulator in the hippocampus, as this AA‐facilitation of the release of the main inhibitory neurotransmitter may predominate under certain circumstances.