Methylene blue induces a dose-dependent elevation in glutamate release but not cGMP levels in cultured neurons

These studies were designed to determine the effect of methylene blue on glutamate release and cGMP elevation. Methylene blue (10-1,000 μM) elevates the extracellular glutamate accumulation in a dose-dependent manner in cultured cerebellar neurons. Super oxide dismutase (SOD, 50 U mL^-1 does not prevent extracellular glutamate accumulation induced by methylene blue or a reducing agent, dithiothreitol (DTT) while SOD suppresses oxygen radical generator (pyrogallol)-induced glutamate accumulation. Cyclic GMP level was highly elevated by sodium nitroprusside (SNP) but not changed by either methylene blue or DTT while the SNP-induced cGMP elevation was strongly prevented by both methylene blue and DTT. Collectively, these results indicate that methylene blue, independently of cGMP elevation, affects glutamate release as a reducing agent.