Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis.
Serotonin (5-HT) stimulated the release of arachidonic acid in hippocampal neurons cocultured with glial cells but not in glial cultures alone. Similar results were observed for the 5-HT-stimulated release of inositol phosphates. These results suggest a neural but not glial origin of both responses. Pharmacological studies suggested that release of arachidonic acid and inositol phosphates was mediated by a type 2 5-HT (5-HT2) receptor. 5-HT-stimulated release of arachidonic acid was also detected in cortical neurons, which contain high levels of 5-HT2 receptors, but not striatum, spinal cord, or cerebellar granule cells, which have very low levels or are devoid of 5-HT2 receptors. The phorbol ester phorbol 12-myristate 13-acetate augmented the 5-HT-stimulated release of arachidonic acid but inhibited the 5-HT-stimulated release of inositol phosphates. 5-HT-stimulated release of arachidonic acid, but not inositol phosphates, was dependent on extracellular calcium. 5-HT stimulated the release of [3H]lysophosphatidylcholine from [3H]choline-labeled cells with no increase in the release of [3H]choline or phospho[3H]choline. These data suggest that 5-HT stimulated the release of arachidonic acid in hippocampal neurons through the activation of phospholipase A2, independent of the activation of phospholipase C.
Felder
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CC
Section on Pharmacology, National Institute of Mental Health, Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, MD 20892.
Kanterman
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RY
Ma
A L
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Axelrod
J
J
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002478:Cells, Cultured; D015777:Eicosanoids / Q000302:isolation & purification / Q000378:metabolism; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*
D001095:Arachidonic Acids; D015777:Eicosanoids; D007295:Inositol Phosphates; D008244:Lysophosphatidylcholines; D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012701:Serotonin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2