title: [Role of hydrogen sulfide, a gasotransmitter, in colonic pain and inflammation].
abstract: Hydrogen sulfide (H2S), the third known gaseous transmitter following nitric oxide and carbon monoxide, is generated by multiple enzymes including cystathionine-γ-lyase (CSE) in vivo. We previously demonstrated that H2S activates Cav3.2 T-type Ca(2+) channels expressed on sensory neurons, leading to hyperalgesia and facilitation of inflammation. Here, we describe the role of H2S in processing of colonic pain and inflammation. Intracolonic (i.col.) administration of NaHS, an H2S donor, to mice evoked colonic pain-like nociceptive behavior and referred hyperalgesia accompanied by phosphorylation of ERK in the superficial layers of spinal dorsal horn, a marker for excitation of nociceptive neurons. The pronociceptive effect of NaHS was abolished by inhibitors or knockdown of Cav3.2 and by an inhibitor of TRPA1, another target molecule of H2S. In rats with colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS), on the other hand, repeated i.col. administration of NaHS prevented colonic ulcer and inflammatory symptoms, which were inhibited by ablation of capsaicin-sensitive sensory neurons or T-type Ca(2+) channel inhibitor. NaHS, given i.col., caused phosphorylation of ERK in the spinal dorsal horn of rats with TNBS-induced colitis, but not of naïve rats. In TNBS-treated rats, Cav3.2 was upregulated in the dorsal root ganglia, while CSE was downregulated in the colon. Taken together, these findings suggest that inhibitors of the CSE/H2S/Cav3.2 or TRPA1 pathways might be useful for the treatment of colonic pain diseases such as irritable bowel syndrome, while H2S donors or Cav3.2 activators might be useful for the treatment of inflammatory bowel disease including Crohn's disease.
authors.affiliation: Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy.
authors.forename: Maho
authors.initials: M
authors.lastname: Tsubota
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D000818:Animals; D003092:Colitis / Q000378:metabolism*; D064426:Gasotransmitters / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D010146:Pain / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D064426:Gasotransmitters; D006862:Hydrogen Sulfide