Polysulfides are possible H2S-derived signaling molecules in rat brain

Accumulating evidence shows that hydrogen sulfide (H2S) has a variety of physiological functions. H2S is produced from cysteine by 3 sulfurtransferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca2+ influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca2+ influx by activating transient receptor potential (TRP) A1 channels in rat astrocytes (EC50 91 nM, Hill coefficient value 1.77 +/- 0.26) and that the maximum response was induced at 0.5 mu M, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 mu M, EC50 116 mu M). TRPA1-selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca2+ influx, and responses to polysulfides were suppressed by TRPA1-selective inhibitors, HC-030031 and AP-18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H2S-derived signaling molecules that stimulate TRP channels in the brain.-Kimura, Y., Mikami, Y., Osumi, K., Tsugane, M., Oka, J., Kimura, H. Polysulfides are possible H2S-derived signaling molecules in rat brain.