文章基本信息

标题：Hydrogen sulfide-induced itch requires activation of Ca_v3.2 T-type calcium channel in mice
本地全文：下载
作者：Xue-Long Wang ; Bin Tian ; Ya Huang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep16768
出版社：Springer Nature
摘要：The contributions of gasotransmitters to itch sensation are largely unknown. In this study, we aimed to investigate the roles of hydrogen sulfide (H₂S), a ubiquitous gasotransmitter, in itch signaling. We found that intradermal injection of H₂S donors NaHS or Na₂S, but not GYY4137 (a slow-releasing H₂S donor), dose-dependently induced scratching behavior in a μ-opioid receptor-dependent and histamine-independent manner in mice. Interestingly, NaHS induced itch via unique mechanisms that involved capsaicin-insensitive A-fibers, but not TRPV1-expressing C-fibers that are traditionally considered for mediating itch, revealed by depletion of TRPV1-expressing C-fibers by systemic resiniferatoxin treatment. Moreover, local application of capsaizapine (TRPV1 blocker) or HC-030031 (TRPA1 blocker) had no effects on NaHS-evoked scratching. Strikingly, pharmacological blockade and silencing of Ca_v3.2 T-type calcium channel by mibefradil, ascorbic acid, zinc chloride or Ca_v3.2 siRNA dramatically decreased NaHS-evoked scratching. NaHS induced robust alloknesis (touch-evoked itch), which was inhibited by T-type calcium channels blocker mibefradil. Compound 48/80-induced itch was enhanced by an endogenous precursor of H₂S (L-cysteine) but attenuated by inhibitors of H₂S-producing enzymes cystathionine γ-lyase and cystathionine β-synthase. These results indicated that H₂S, as a novel nonhistaminergic itch mediator, may activates Ca_v3.2 T-type calcium channel, probably located at A-fibers, to induce scratching and alloknesis in mice.