Facilitation of GABA release by arachidonic acid in rat hippocampal synaptosomes.
Arachidonic acid (AA) is proposed to be a facilitatory retrograde messenger in hippocampal glutamatergic synapses. In this study, we found that AA (10 microM) increased the basal outflow (19 +/- 4%) and the K+-evoked release of [3H]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 microM) and was not modified by inhibition of either lipooxygenase with nordihydroguaiaretic acid (50 microM) or cyclooxygenase with indomethacin (100 microM). Activation of protein kinase C may be involved, as chelerythrine (6 microM), a protein kinase C inhibitor, attenuated the AA (10 microM)-facilitation of K+-evoked [3H]GABA release by 58 +/- 5%. Phospholipase A2 (2 U/mL), an enzyme that releases AA, and melittin (1 microM), a phospholipase A2 activator, mimicked the AA-facilitation of evoked [3H]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 [3H]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.
Cunha
R A
RA
Laboratory of Neurosciences, Faculty of Medicine, Department of Chemistry and Biochemistry, University of Lisbon, Lisboa, Portugal. racunha@neurosciencias.pt
Ribeiro
J A
JA
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D016718:Arachidonic Acid; D005680:gamma-Aminobutyric Acid