Dombkowski Ryan A, Doellman Meredith M, Head Sally K, Olson Kenneth R
South Bend Center for Medical Education, Indiana University School of Medicine, University of Notre Dame, Notre Dame, IN 46556, USA.
J Exp Biol. 2006 Aug;209(Pt 16):3234-40. doi: 10.1242/jeb.02376.
Hydrogen sulfide (H2S) is a recently identified gasotransmitter that may mediate hypoxic responses in vascular smooth muscle. H2S also appears to be a signaling molecule in mammalian non-vascular smooth muscle, but its existence and function in non-mammalian non-vascular smooth muscle have not been examined. In the present study we examined H2S production and its physiological effects in urinary bladder from steelhead and rainbow trout (Oncorhynchus mykiss) and evaluated the relationship between H2S and hypoxia. H2S was produced by trout bladders, and its production was sensitive to inhibitors of cystathionine beta-synthase and cystathionine gamma-lyase. H2S produced a dose-dependent relaxation in unstimulated and carbachol pre-contracted bladders and inhibited spontaneous contractions. Bladders pre-contracted with 80 mmol l(-1) KCl were less sensitive to H2S than bladders contracted with either 80 mmol l(-1) KC2H3O2 (KAc) or carbachol, suggesting that some of the H2S effects are mediated through an ion channel. However, H2S relaxation of bladders was not affected by the potassium channel inhibitors, apamin, charybdotoxin, 4-aminopyridine, and glybenclamide, or by chloride channel/exchange inhibitors 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt, tamoxifen and glybenclamide, or by the presence or absence of extracellular HCO3-. Inhibitors of neuronal mechanisms, tetrodotoxin, strychnine and N-vanillylnonanamide were likewise ineffective. Hypoxia (aeration with N2) also relaxed bladders, was competitive with H2S for relaxation, and it was equally sensitive to KCl, and unaffected by neuronal blockade or the presence of extracellular HCO3-. Inhibitors of H2S synthesis also inhibited hypoxic relaxation. These experiments suggest that H2S is a phylogenetically ancient gasotransmitter in non-mammalian non-vascular smooth muscle and that it serves as an oxygen sensor/transducer, mediating the effects of hypoxia.
硫化氢（H₂S）是一种最近被发现的气体信号分子，它可能介导血管平滑肌中的缺氧反应。H₂S在哺乳动物非血管平滑肌中似乎也是一种信号分子，但它在非哺乳动物非血管平滑肌中的存在和功能尚未得到研究。在本研究中，我们检测了虹鳟和硬头鳟（Oncorhynchus mykiss）膀胱中H₂S的产生及其生理效应，并评估了H₂S与缺氧之间的关系。鳟鱼膀胱能产生H₂S，其产生对胱硫醚β-合酶和胱硫醚γ-裂合酶抑制剂敏感。H₂S在未受刺激和用卡巴胆碱预收缩的膀胱中产生剂量依赖性舒张，并抑制自发收缩。用80 mmol l⁻¹ KCl预收缩的膀胱对H₂S的敏感性低于用80 mmol l⁻¹ KC₂H₃O₂（KAc）或卡巴胆碱收缩的膀胱，这表明H₂S的一些效应是通过离子通道介导的。然而，膀胱的H₂S舒张不受钾通道抑制剂蜂毒明肽、蝎毒素、4-氨基吡啶和格列本脲的影响，也不受氯通道/交换抑制剂4,4'-二异硫氰酸根合芪-2,2'-二磺酸二钠盐、他莫昔芬和格列本脲的影响，也不受细胞外HCO₃⁻存在与否的影响。神经机制抑制剂河豚毒素、士的宁和N-香草基壬酰胺同样无效。缺氧（用N₂通气）也能使膀胱舒张，与H₂S舒张具有竞争性，并且对KCl同样敏感，不受神经阻断或细胞外HCO₃⁻存在的影响。H₂S合成抑制剂也抑制缺氧性舒张。这些实验表明，H₂S是一种在非哺乳动物非血管平滑肌中具有系统发育古老性的气体信号分子，它作为一种氧传感器/转换器，介导缺氧的效应。
