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

After incubation of highly enriched neurons from rat cerebral cortex w ith 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 r eact 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 cytoto xicity. Administration of mepacrine reduced cytotoxicity caused by gp1 20. 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.