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Exposure to gp120 of HIV‐1 Induces an Increased Release of Arachidonic Acid in Rat Primary Neuronal Cell Culture Followed by NMDA Receptor‐mediated Neurotoxicity
Author(s) -
Ushijima Hiroshi,
Nishio Osamu,
Klöcking Renate,
Perovic Sanja,
Müller Werner E.G.
Publication year - 1995
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.1460-9568.1995.tb01126.x
Subject(s) - nmda receptor , neurotoxicity , arachidonic acid , cytotoxicity , agonist , phospholipase a2 , receptor , pharmacology , chemistry , phospholipase a , biology , biochemistry , in vitro , toxicity , enzyme , organic chemistry
After incubation of highly enriched neurons from rat cerebral cortex with the HIV‐1 coat protein gp120 for 18 h, cells showed fragmentation of DNA at internucleosomal linkers followed by NMDA receptor‐mediated neurotoxicity. We report that in response to exposure to gp120 cells react with an increased release of arachidonic acid (AA) via activation of phospholipase A 2 . This process was not inhibited by NMDA receptor antagonists. To investigate the role of AA on the sensitivity of the NMDA receptor towards its agonist, low concentrations of NMDA were co‐administered with AA. This condition enhanced the NMDA‐mediated cytotoxicity. Administration of mepacrine reduced cytotoxicity caused by gp120. We conclude that gp120 causes an activation of phospholipase A 2 , resulting in the increased release of AA, which may in turn sensitize the NMDA receptor.