P78: Polysulfides are possible H2S-derived signaling molecules in rat brain

Abstract

Accumulating evidence shows that hydrogen sulfide (H 2 S) has a variety of physiological functions. H 2 S is produced from cysteine by 3 sulfurtransferases. H 2 S, in turn, generates polysulfides, the functions of which are not well understood. H 2 S induces Ca 2+ 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 Ca 2+ 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 microM, which is 1/320 of the concentration of H 2 S required to achieve a response of similar magnitude (160 microM, EC50 116 microM). TRPA1-selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca 2+ 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 H 2 S -derived signaling molecules that stimulate TRP channels in the brain.