The possible role of hydrogen sulfide as an endogenous neuromodulator

The possible role of hydrogen sulfide as an endogenous neuromodulator
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DOI:
10.1523/jneurosci.16-03-01066.1996
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发表时间:
1996-02
期刊:
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影响因子:
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通讯作者:
K. Abe;H. Kimura
K. Abe;H. Kimura
中科院分区:
其他
文献类型:
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作者:
K. Abe;H. Kimura

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硫化氢(H2S)是哺乳动物组织中L-半胱氨酸内源性产生的有毒气体。H2S在大脑中的含量相对较高,这表明它具有生理功能。另外两种气体,一氧化氮和一氧化碳,也是内源性产生的,被认为是大脑中的神经信使。在这项工作中,我们显示了以下内容:(1)H2S产生酶,胱硫醚β-合成酶(CBS),在海马体中高度表达;(2)CBS抑制剂羟胺和氨基氧乙酸抑制脑H2S的产生;(3)CBS激活剂,S-腺苷-L-甲硫氨酸,增强H2S的产生,表明CBS有助于内源性H2S的产生。我们还表明,生理浓度的硫化氢选择性地增强NMDA受体介导的反应,促进诱导海马长时程增强。这些观察结果表明,内源性H2S在大脑中起神经调质的作用。
Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced endogenously from L-cysteine in mammalian tissues. H2S is present at relatively high levels in the brain, suggesting that it has a physiological function. Two other gases, nitric oxide and carbon monoxide, are also endogenously produced and have been proposed as neuronal messengers in the brain. In this work we show the following: (1) an H2S-producing enzyme, cystathionine beta-synthase (CBS), is highly expressed in the hippocampus; (2) CBS inhibitors hydroxylamine and amino-oxyacetate suppress the production of brain H2S; and (3) a CBS activator, S-adenosyl-L-methionine, enhances H2S production, indicating that CBS contributes to the production of endogenous H2S. We also show that physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and facilitate the induction of hippocampal long-term potentiation. These observations suggest that endogenous H2S functions as a neuromodulator in the brain.