LACK OF CORRELATION BETWEEN GLUTAMATE-INDUCED DEPLETION OF ATP AND NEURONAL DEATH IN PRIMARY CULTURES OF CEREBELLUM

The aim of this work was to identify, using primary cultures of cerebe llar neurons, the receptors involved in glutamate-induced depletion of ATP and to assess whether there is a correlation between glutamate-in duced ATP depletion and neuronal death. Glutamate induced a rapid depl etion of ATP (40% decrease at 5 min). After 60 min incubation with 1 m M glutamate ATP content decreased by 60-70%. Similar effects were indu ced by glutamate, NMDA and kainate while quisqualate, AMPA or trans-AC PD did not affect significantly ATP content. The EC(50) were approxima te to 6, 25 and 30 mu M for glutamate, NMDA and kainate, respectively. DNQX and AP-5, competitive antagonists of kainate and NMDA receptors, respectively, prevented in a dose-dependent manner the glutamate-indu ced depletion of ATP. These results indicate that glutamate-induced de pletion of ATP is mediated by activation of kainate and NMDA receptors . Glutamate-induced neuronal death was prevented by MK-801, calphostin C, H7, carnitine, nitroarginine and W7. However, only MK-801 and W7 p revented glutamate-induced depletion of ATP, while calphostin C, H7, c arnitine and nitroarginine did not. This indicates that there is not a direct correlation between ATP depletion and neuronal death.