Physiological roles of hydrogen sulfide: synaptic modulation, neuroprotection, and smooth muscle relaxation.

Nearly 300 years have passed since the first description of the toxicity of hydrogen sulfide (H(2)S) in 1713. Although many studies have been devoted to its toxicity, very little attention has been paid to understanding its normal physiological function. Relatively high concentrations of endogenous H(2)S, however, have recently been discovered in animal tissues, and its possible function as a biological messenger has been proposed. H(2)S enhances the activity of N-methyl-D-aspartate receptors and facilitates the induction of hippocampal longterm potentiation, a synaptic model for memory. H(2)S also increases intracellular concentrations of Ca(2+) in glia and induces Ca(2+) waves, which mediate glial signal transmission. Based on accumulating evidence for the reciprocal interactions between glia and neurons, it has been suggested that glia modulate synaptic transmission. Therefore, H(2)S may regulate synaptic activity by modulating the activity of both neurons and glia. In addition to a role in the signal transduction, H(2)S protects neurons from oxidative stress and in smooth muscle it may function as a relaxant. H(2)S, the toxic gas, may therefore be used as a multifunctional signaling mechanism under normal physiological conditions.