EFFECTS OF GUANINE-NUCLEOTIDES ON GLUTAMATE-INDUCED CHEMILUMINESCENCEIN RAT HIPPOCAMPAL SLICES SUBMITTED TO HYPOXIA

Glutamate significantly increased levels of spontaneous chemiluminesce nce (CL) in rat hippocampal slices incubated under hypoxic conditions. Although it has been previously shown that guanine nucleotides (GN) d isplace glutamate from several of its receptors, in our study only GMP , as well as the glutamate antagonist MK-801, was able to reverse the increase in CL provoked by glutamate. On the other hand, not only GTP or Gpp(NH)p failed to reverse the action of glutamate, but they increa sed CL production like glutamate. This effect of GTP/Gpp(NH)p was also reversed by GMP. We concluded that, under neurotoxic conditions, GMP acted as an antagonist and GTP or Gpp(NH)p acted as agonists of glutam ate. These results reinforced the evidence of the existence of extrace llular site(s) for GN and indicated a possible role for GN in excitoto xicity.