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Effect of Glutamate and lonomycin on the Release of Arachidonic Acid, Prostaglandins and HETEs from Cultured Neurons and Astrocytes
Author(s) -
Oomagari Kiyoshi,
Buisson Bruno,
Dumuis Aline,
Bockaert Joël,
Pin JeanPhilippe
Publication year - 1991
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 - 10.1111/j.1460-9568.1991.tb00028.x
Subject(s) - ionomycin , arachidonic acid , astrocyte , glutamate receptor , hydroxyeicosatetraenoic acid , metabolism , biology , biochemistry , neuroglia , cyclooxygenase , endocrinology , stimulation , medicine , chemistry , central nervous system , enzyme , receptor
The release of arachidonic acid (ArA) metabolites from mouse neurons and astrocytes in primary culture has been studied in response to ionomycin or glutamate stimulation. Cells were preincubated with [ 3 H] ArA for 24 h and the radioactivity released was examined by HPLC. In striatal, cortical and hippocampal neurons, glutamate and ionomycin strongly stimulated the release of ArA, but neither prostaglandins (PGs) nor hydroxyeicosatetraenoic acids (HETEs) could be detected. If they were released, these latter compounds represented < 0.02% of the amount of ArA. In contrast, in astrocyte cultures, ionomycin (but not glutamate) strongly stimulated the release of PGs and HETEs as well as ArA. Reversed‐ and straight‐phase HPLC analysis revealed the presence of PGD 2 , PGE 2 , PGF 2α , 12‐hydroxyheptadeca‐5, 8,10‐trienoic acid (HHT) and HETEs (15‐HETE, 11‐HETE and 5‐HETE). Indomethacin inhibited the release of PGs and HHT, but also that of 11‐ and 15‐HETE, indicating that these two HETEs may be produced through the cyclooxygenase pathway. Metabolism of [ 3 H]ArA was also examined in cellular homogenates. Although > 50% of the [ 3 H]ArA was metabolized to PGF 2α , PGE 2 , PGD 2 , HHT, 15‐ and 11‐HETE in cultured astrocyte homogenates, no [ 3 H]ArA metabolism could be detected in cultured striatal neuron homogenates. Moreover, neuronal homogenates did not inhibit the metabolism of [ 3 H]ArA observed in either astrocyte or platelet homogenates. These results indicate that central neurons in primary culture possess very low lipoxygenase and cyclooxygenase activities. They emphasize the need to identify the cellular source of ArA metabolites in the brain, particularly when considering the multiple new messenger roles proposed for these molecules, such as that of retrograde messengers involved in synaptic plasticity phenomena.