Polysulfides are possible H2S-derived signaling molecules in rat brain

FASEB J. 2013 Jun;27(6):2451-7. doi: 10.1096/fj.12-226415. Epub 2013 Feb 14.

Abstract

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 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 μM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 μM, EC50 116 μM). 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 H2S-derived signaling molecules that stimulate TRP channels in the brain.

Keywords: Ca2+ influx; TRP channels; hydrogen sulfide; persulfide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology
  • Acrolein / analogs & derivatives
  • Acrolein / pharmacology
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Brain / metabolism*
  • Calcium Signaling / drug effects
  • Gadolinium / pharmacology
  • Hydrogen Sulfide / metabolism*
  • Isothiocyanates / pharmacology
  • Lanthanum / pharmacology
  • Male
  • Mice
  • Purines / pharmacology
  • RNA, Small Interfering / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Ruthenium Red / pharmacology
  • Signal Transduction
  • Sulfides / metabolism*
  • TRPA1 Cation Channel
  • TRPC Cation Channels / agonists
  • TRPC Cation Channels / antagonists & inhibitors
  • TRPC Cation Channels / metabolism*

Substances

  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • Acetanilides
  • Isothiocyanates
  • Purines
  • RNA, Small Interfering
  • Sulfides
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • Trpa1 protein, rat
  • Ruthenium Red
  • Lanthanum
  • Acrolein
  • polysulfide
  • Gadolinium
  • allyl isothiocyanate
  • cinnamic aldehyde
  • Hydrogen Sulfide