GLUTAMATE TOXICITY IN PRIMARY CEREBELLAR CULTURES FROM MOUSE-BRAIN ISUNAFFECTED BY CHANGES IN CGMP LEVELS

DURING evaluation of potential end-points for in vitro neurotoxicity s creening we investigated what influence changes in cyclic GMP (cGMP) l evels might exert on the degree of glutamate (Glu)-induced neurotoxici ty in primary cultures of mouse cerebellar granule cells. Depletion of Glu-stimulated cGMP levels by N-methyl-D-aspartate receptor antagonis ts fully protected against Glu-induced toxicity. However, when Glu-sti mulated cGMP levels were either depleted or elevated by the use of a v ariety of pharmacological agents acting intracellularly at various poi nts of the NO/cGMP signalling pathway the degree of cytotoxicity exert ed by Glu was unaltered. These results imply that cGMP and NO do not m odulate the toxic effects of Glu and are therefore unsuitable as bioma rkers of excitotoxicity in these cells.