氣態神經遞質

氣態神經遞質（英語：Gasotransmitter）是一類神經傳導物質。這些分子與其他生物活性內源性氣體訊號分子的差異在於需要滿足不同的表徵標準。目前，只有一氧化氮、一氧化碳和硫化氫被接受為氣態神經遞質。 根據體外模型 (英語：In Vitro Model)，氣體傳導物質與其他氣體訊號分子一樣，可能與氣體感受器結合並觸發細胞中的訊號傳導。 氣態神經遞質這個名稱並不意味著氣態物理狀態，例如無限小的氣泡；物理狀態是溶解在複雜的體液和細胞質中。這些特殊氣體在其生產和功能上具有許多共同特徵，但以不同於經典訊號分子的獨特方式執行其任務。 "氣態神經遞質"的術語和表徵準則於2002年首次引入。對於一種被歸類為氣態神經遞質的氣體分子，應符合以下所有準則。 它是一種小分子氣體； 它可自由滲透膜。因此，其作用不依賴同源膜受體。它可以具有內分泌、旁分泌和自分泌作用。例如，在內分泌作用模式下，氣態神經遞質可以進入血流；被清道夫攜帶到遠端目標並釋放在那裡，調節遠端目標細胞的功能； 它是內源性酵素產生的，其產生受到調節； 它在生理相關濃度下具有明確且特定的功能。因此，控制這種氣體的內源水平會引起特定的生理變化。 這種內源性氣體的功能可以透過其外源性應用的對應物來模仿； 其細胞效應可能由第二信使介導，也可能不由第二信使介導，但應具有特定的細胞和分子標靶。 諷刺的是，目前的氣體遞質“三位一體”，即一氧化氮、一氧化碳和硫化氫，在歷史上一直被當作無用的有毒氣體而丟棄。這些分子是劑量依賴性毒物兴奋效应的典型例子，低劑量是有益的，而缺乏或過量劑量則是有毒的。這些內源性分子的有益作用激發了每種氣體的重大藥物開發工作。 這三種氣體具有許多相似的特徵，並參與共享的信號傳導途徑，儘管它們的作用可以是協同的，也可以作為拮抗劑。一氧化氮和硫化氫與許多分子標靶高度反應，而一氧化碳相對穩定且代謝惰性，主要限於與哺乳動物體內的亞鐵離子複合物相互作用。 然而，不同系統發育界的生物功能範圍有所不同，一氧化碳與鎳或鉬一氧化碳脱氢酶的重要交互作用就是例證。 氣態神經遞質正在接受以下學科的研究：生物传感、免疫學、神經科學、胃腸病學、和許多其他領域包括藥物開發措施。雖然生物醫學研究受到了最多的關注，但整個生物界都在研究氣態神經遞質。 已經開發了許多分析工具來協助氣體遞質的研究。 Mustafa AK, Gadalla MM, Snyder SH. Signaling by gasotransmitters. Science Signaling. April 2009, 2 (68): re2. PMC 2744355 . PMID 19401594. doi:10.1126/scisignal.268re2.  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.  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 .  Wang R (ed) (2004) Signal Transduction and the Gasotransmitters: NO, CO and H2S in Biology and Medicine. Humana Press, New Jersey, USA. 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 . PMID 22615409. doi:10.1073/pnas.1206646109 .  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 .  Motterlini R, Foresti R. Biological signaling by carbon monoxide and carbon monoxide-releasing molecules. American Journal of Physiology. Cell Physiology. March 2017, 312 (3): C302–C313. PMID 28077358. S2CID 21861993. doi:10.1152/ajpcell.00360.2016 .  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 . PMID 30190328. doi:10.1042/BST20170311.  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.  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.  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.  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.  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 . PMID 33781582. doi:10.1016/j.tips.2021.02.003.  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.  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 . PMID 25996214. doi:10.3390/molecules20059099 .  Liu T, Mukosera GT, Blood AB. The role of gasotransmitters in neonatal physiology. Nitric Oxide. February 2020, 95: 29–44. PMC 7241003 . PMID 31870965. doi:10.1016/j.niox.2019.12.002.  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 . PMID 23992228. doi:10.1111/apt.12467.  引用错误：没有为名为:0的参考文献提供内容 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.  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 . PMID 25891246. doi:10.1111/bph.13005.  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.  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）.  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 . PMID 32792988. doi:10.3389/fphys.2020.00886 .  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 . PMID 27389418. doi:10.3402/mehd.v27.30971.  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）.  （英文）European Network on Gasotransmitters (ENOG) （页面存档备份，存于互联网档案馆）