Metabolites of arachidonic acid in the nervous system of Aplysia: possible mediators of synaptic modulation.
Release of arachidonic acid from membrane phospholipids is receptor-mediated and might generate second messengers in neurons. We tested this idea using the simple nervous system of the marine mollusk, Aplysia californica. Aplysia neural components metabolize arachidonic acid through lipoxygenase and cyclo-oxygenase pathways. We identified 2 major lipoxygenase products, 12- and 5-hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and 2 cyclo-oxygenase products, PGE2 and PGF2 alpha. These metabolites of arachidonic acid are formed in synaptosomes, as well as in identified nerve cell bodies, indicating that both lipoxygenase and cyclo-oxygenase pathways are active within neurons. Application of the modulatory neurotransmitter histamine to cerebral ganglia that had been labeled with 3H-arachidonic acid induced the formation of 3H-12-HETE. This response was inhibited by the histamine antagonist cimetidine. Furthermore, release of radioactive 5-HETE and 12-HETE was observed after intracellular stimulation of the histaminergic cell C2 in cerebral ganglia labeled with 3H-arachidonic acid. Cimetidine also inhibited this response. Application of serotonin or stimulation of the giant serotonergic cell (GCN) in the cerebral ganglion did not cause detectable amounts of the labeled eicosanoids to be released. We found that intracellular stimulation of putative histaminergic neurons in the L32 cluster of the abdominal ganglion, which produces presynaptic inhibition in L10 neurons, also elicited the release of 3H-12-HETE and 3H-PGE2. Thus, for the first time we provide evidence that synaptic stimulation promotes turnover of arachidonic acid in neurons. We suggest that metabolites of arachidonic acid are likely to participate in some postsynaptic responses to histamine and may be second messengers for presynaptic inhibition.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001048:Aplysia / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D004558:Electric Stimulation; D005227:Fatty Acids / Q000032:analysis; D006632:Histamine / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
D001095:Arachidonic Acids; D005227:Fatty Acids; D006893:Hydroxyeicosatetraenoic Acids; D008563:Membrane Lipids; D010743:Phospholipids; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D006632:Histamine; D011451:Prostaglandin-Endoperoxide Synthases