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气态神经递质

维基百科，自由的百科全书

气态神经递质（英语：Gasotransmitter）是一类神经传导物质。这些分子与其他生物活性内源性气体讯号分子的差异在于需要满足不同的表征标准。目前，只有一氧化氮、一氧化碳和硫化氢被接受为气态神经递质。[1] 根据体外模型 (英语：In Vitro Model)，气体传导物质与其他气体讯号分子一样，可能与气体感受器结合并触发细胞中的讯号传导。[1]

气态神经递质这个名称并不意味著气态物理状态，例如无限小的气泡；物理状态是溶解在复杂的体液和细胞质中。[2]这些特殊气体在其生产和功能上具有许多共同特征，但以不同于经典讯号分子的独特方式执行其任务。

准则

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"气态神经递质"的术语和表征准则于2002年首次引入。[3]对于一种被归类为气态神经递质的气体分子，应符合以下所有准则。[4][3]

  1. 它是一种小分子气体；
  2. 它可自由渗透膜。因此，其作用不依赖同源膜受体。它可以具有内分泌、旁分泌和自分泌作用。例如，在内分泌作用模式下，气态神经递质可以进入血流；被清道夫携带到远端目标并释放在那里，调节远端目标细胞的功能；
  3. 它是内源性酵素产生的，其产生受到调节；
  4. 它在生理相关浓度下具有明确且特定的功能。因此，控制这种气体的内源水平会引起特定的生理变化。
  5. 这种内源性气体的功能可以透过其外源性应用的对应物来模仿；
  6. 其细胞效应可能由第二信使介导，也可能不由第二信使介导，但应具有特定的细胞和分子标靶。

概述

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讽刺的是，目前的气体递质“三位一体”，即一氧化氮、一氧化碳和硫化氢，在历史上一直被当作无用的有毒气体而丢弃。这些分子是剂量依赖性毒物兴奋效应的典型例子，低剂量是有益的，而缺乏或过量剂量则是有毒的。这些内源性分子的有益作用激发了每种气体的重大药物开发工作。

这三种气体具有许多相似的特征，并参与共享的信号传导途径，尽管它们的作用可以是协同的，也可以作为拮抗剂。[5][6]一氧化氮和硫化氢与许多分子标靶高度反应，而一氧化碳相对稳定且代谢惰性，主要限于与哺乳动物体内的亚铁离子复合物相互作用。[7] 然而，不同系统发育界的生物功能范围有所不同，一氧化碳与镍或钼一氧化碳脱氢酶的重要交互作用就是例证。[8]

气态神经递质正在接受以下学科的研究：生物传感[9][10]、免疫学[11][12]、神经科学[13][14]、胃肠病学[15][16][17]、和许多其他领域包括药物开发措施。[18][19][20]虽然生物医学研究受到了最多的关注，但整个生物界都在研究气态神经递质。[21][22][23][24]

已经开发了许多分析工具来协助气体递质的研究。[25]

参考文献

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  1. ^ 1.0 1.1 Mustafa AK, Gadalla MM, Snyder SH. Signaling by gasotransmitters. Science Signaling. April 2009, 2 (68): re2. PMC 2744355 可免费查阅. PMID 19401594. doi:10.1126/scisignal.268re2. 
  2. ^ Simpson PV, Schatzschneider U. Release of Bioactive Molecules Using Metal Complexes. Gasser G (编). Inorganic Chemical Biology. Chichester, UK: John Wiley & Sons, Ltd. 2014-04-18: 309–339. ISBN 978-1-118-68297-5. doi:10.1002/9781118682975.ch10. 
  3. ^ 3.0 3.1 Wang R. Two's company, three's a crowd: can H2S be the third endogenous gaseous transmitter?. FASEB Journal. November 2002, 16 (13): 1792–1798. PMID 12409322. S2CID 40765922. doi:10.1096/fj.02-0211hyp 可免费查阅. 
  4. ^ Wang R (ed) (2004) Signal Transduction and the Gasotransmitters: NO, CO and H2S in Biology and Medicine. Humana Press, New Jersey, USA.
  5. ^ Wang R. Shared signaling pathways among gasotransmitters. Proceedings of the National Academy of Sciences of the United States of America. June 2012, 109 (23): 8801–2. Bibcode:2012PNAS..109.8801W. PMC 3384202 可免费查阅. PMID 22615409. doi:10.1073/pnas.1206646109 可免费查阅. 
  6. ^ Hendriks KD, Maassen H, van Dijk PR, Henning RH, van Goor H, Hillebrands JL. Gasotransmitters in health and disease: a mitochondria-centered view. Current Opinion in Pharmacology. April 2019, 45: 87–93. PMID 31325730. S2CID 198135525. doi:10.1016/j.coph.2019.07.001 可免费查阅. 
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  8. ^ Wareham LK, Southam HM, Poole RK. Do nitric oxide, carbon monoxide and hydrogen sulfide really qualify as 'gasotransmitters' in bacteria?. Biochemical Society Transactions. October 2018, 46 (5): 1107–1118. PMC 6195638 可免费查阅. PMID 30190328. doi:10.1042/BST20170311. 
  9. ^ Shimizu T, Lengalova A, Martínek V, Martínková M. Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres. Chemical Society Reviews. December 2019, 48 (24): 5624–5657. PMID 31748766. S2CID 208217502. doi:10.1039/C9CS00268E. 
  10. ^ Shimizu T, Huang D, Yan F, Stranava M, Bartosova M, Fojtíková V, Martínková M. Gaseous O2, NO, and CO in signal transduction: structure and function relationships of heme-based gas sensors and heme-redox sensors. Chemical Reviews. July 2015, 115 (13): 6491–6533. PMID 26021768. doi:10.1021/acs.chemrev.5b00018. 
  11. ^ Campbell NK, Fitzgerald HK, Dunne A. Regulation of inflammation by the antioxidant haem oxygenase 1. Nature Reviews. Immunology. July 2021, 21 (7): 411–425. PMID 33514947. S2CID 231762031. doi:10.1038/s41577-020-00491-x. 
  12. ^ Fagone P, Mazzon E, Bramanti P, Bendtzen K, Nicoletti F. Gasotransmitters and the immune system: Mode of action and novel therapeutic targets. European Journal of Pharmacology. September 2018, 834: 92–102. PMID 30016662. S2CID 51679533. doi:10.1016/j.ejphar.2018.07.026. 
  13. ^ Siracusa R, Schaufler A, Calabrese V, Fuller PM, Otterbein LE. Carbon Monoxide: from Poison to Clinical Trials. Trends in Pharmacological Sciences. May 2021, 42 (5): 329–339. PMC 8134950 可免费查阅. PMID 33781582. doi:10.1016/j.tips.2021.02.003. 
  14. ^ Singh S. Updates on Versatile Role of Putative Gasotransmitter Nitric Oxide: Culprit in Neurodegenerative Disease Pathology. ACS Chemical Neuroscience. August 2020, 11 (16): 2407–2415. PMID 32564594. S2CID 219973120. doi:10.1021/acschemneuro.0c00230. 
  15. ^ Magierowski M, Magierowska K, Kwiecien S, Brzozowski T. Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity, protection and ulcer healing. Molecules. May 2015, 20 (5): 9099–9123. PMC 6272495 可免费查阅. PMID 25996214. doi:10.3390/molecules20059099 可免费查阅. 
  16. ^ Liu T, Mukosera GT, Blood AB. The role of gasotransmitters in neonatal physiology. Nitric Oxide. February 2020, 95: 29–44. PMC 7241003 可免费查阅. PMID 31870965. doi:10.1016/j.niox.2019.12.002. 
  17. ^ Gibbons SJ, Verhulst PJ, Bharucha A, Farrugia G. Review article: carbon monoxide in gastrointestinal physiology and its potential in therapeutics. Alimentary Pharmacology & Therapeutics. October 2013, 38 (7): 689–702. PMC 3788684 可免费查阅. PMID 23992228. doi:10.1111/apt.12467. 
  18. ^ 引用错误：没有为名为:0的参考文献提供内容
  19. ^ Wallace JL, Wang R. Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter. Nature Reviews. Drug Discovery. May 2015, 14 (5): 329–345. PMID 25849904. S2CID 5361233. doi:10.1038/nrd4433. 
  20. ^ Papapetropoulos A, Foresti R, Ferdinandy P. Pharmacology of the 'gasotransmitters' NO, CO and H2S: translational opportunities. British Journal of Pharmacology. March 2015, 172 (6): 1395–1396. PMC 4369252 可免费查阅. PMID 25891246. doi:10.1111/bph.13005. 
  21. ^ Imbrogno S, Filice M, Cerra MC, Gattuso A. NO, CO and H2 S: What about gasotransmitters in fish and amphibian heart?. Acta Physiologica. May 2018, 223 (1): e13035. PMID 29338122. S2CID 4793586. doi:10.1111/apha.13035. 
  22. ^ Kolupaev YE, Karpets YV, Beschasniy SP, Dmitriev AP. Gasotransmitters and Their Role in Adaptive Reactions of Plant Cells. Cytology and Genetics. 2019-09-01, 53 (5): 392–406. ISSN 1934-9440. S2CID 208605375. doi:10.3103/S0095452719050098 （英语）. 
  23. ^ Tift MS, Alves de Souza RW, Weber J, Heinrich EC, Villafuerte FC, Malhotra A, Otterbein LE, Simonson TS. Adaptive Potential of the Heme Oxygenase/Carbon Monoxide Pathway During Hypoxia. Frontiers in Physiology. 2020-07-22, 11: 886. PMC 7387684 可免费查阅. PMID 32792988. doi:10.3389/fphys.2020.00886 可免费查阅. 
  24. ^ Oleskin AV, Shenderov BA. Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota. Microbial Ecology in Health and Disease. 2016-07-05, 27: 30971. PMC 4937721 可免费查阅. PMID 27389418. doi:10.3402/mehd.v27.30971. 
  25. ^ Peng H, Chen W, Wang B. Methods for the Detection of Gasotransmitters. Hermann A, Sitdikova GF, Weiger TM (编). Gasotransmitters: Physiology and Pathophysiology. Berlin, Heidelberg: Springer. July 2012: 99–137. ISBN 978-3-642-30338-8. doi:10.1007/978-3-642-30338-8_4 （英语）. 

外部链接

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