Hydrogen sulfide is a reversible inhibitor of the NADH oxidase activity of synaptic plasma membranes

Hydrogen sulfide is now accepted as a neuromodulator, which can be involved in neuronal defence against oxidative stress insults in the brain. In this work we show that concentrations of H2S within the physiological range reported in the brain produce a reversible inhibition of the NADH oxidase activity and coupled superoxide anion production by synaptic plasma membranes from rat brain. At physiological pH 7 the concentration of H2S needed for 50% inhibition of the NADH oxidase activity is 5 ± 1 μM, which is within the low range of the reported physiological H2S concentrations. Thus, the NADH oxidase activity of the neuronal plasma membrane can act as a sensor of local H2S depletion in neurones. H2S inhibition of the NADH oxidase activity of the neuronal plasma membrane can be accounted for direct reduction by H2S of cytochrome b5. However, H2S fails to afford a significant protection against the inhibition of this activity by peroxynitrite. In conclusion, our results point out that H2S is more potent as inhibitor of reactive oxygen species formation than as a sacrificial antioxidant.