Cs. Malcolm et al., GLUTAMATE TOXICITY IN PRIMARY CEREBELLAR CULTURES FROM MOUSE-BRAIN ISUNAFFECTED BY CHANGES IN CGMP LEVELS, NeuroReport, 7(10), 1996, pp. 1650-1654
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.