Hypoxia releases S-nitrosocysteine from carotid body glomus cells-relevance to expression of the hypoxic ventilatory response.
Hypoxia releases S-nitrosocysteine from carotid body glomus cells-relevance to expression of the hypoxic ventilatory response.
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DOI：
10.3389/fphar.2023.1250154
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
我们提供了间接的药理学证据，证明低氧可引起大鼠原代颈动脉体球细胞释放S-亚硝硫醇、S-亚硝基-L-半胱氨酸(L-CSNO)，进而激活颈动脉窦神经的化学感受性传入，从而引起低氧呼吸机能反应。本研究的目的是利用我们的电容式S-亚硫醇传感器提供直接证据，证明从雄性SD大鼠颈动脉小体提取的PGCs中储存和释放了L-CSNO，从而为S-亚硝硫醇在介导高压反应中的作用提供了进一步的药理学证据。本研究的主要发现是：1)PGCs裂解产物中含有一种理化性质与L-CSNO相似的S-亚硝硫醇，而不是S-亚硝基-L-谷胱甘肽(L-GSNO)；2)低氧刺激使PGCs灌流液中S-亚硫醇浓度显著增加，达到接近100fm的水平，这是通过需要细胞外钙离子的机制实现的；3)动脉注射L-CSNO和L-GSNO引起的分钟通气量增加可能是由于激活了小直径无髓C纤维体传入的颈动脉，4)L-CSNO，而不是L-GSNO，而不是L-GSNO静脉注射S-甲基-L-半胱氨酸(10μ/kg/min，IV)和S-乙基-L-半胱氨酸(L-Sec)可显著降低大鼠对低氧气体刺激(10%O2，90%N_2)的呼吸性反应。这一结果为大鼠PGCs合成一种S-亚硫醇提供了证据，该亚硫醇的性质与L-CSNO相似，在低氧条件下以细胞外钙依赖的方式释放。
We have provided indirect pharmacological evidence that hypoxia may trigger release of the S-nitrosothiol, S-nitroso-L-cysteine (L-CSNO), from primary carotid body glomus cells (PGCs) of rats that then activates chemosensory afferents of the carotid sinus nerve to elicit the hypoxic ventilatory response (HVR). The objective of this study was to provide direct evidence, using our capacitive S-nitrosothiol sensor, that L-CSNO is stored and released from PGCs extracted from male Sprague Dawley rat carotid bodies, and thus further pharmacological evidence for the role of S-nitrosothiols in mediating the HVR. Key findings of this study were that 1) lysates of PGCs contained an S-nitrosothiol with physico-chemical properties similar to L-CSNO rather than S-nitroso-L-glutathione (L-GSNO), 2) exposure of PGCs to a hypoxic challenge caused a significant increase in S-nitrosothiol concentrations in the perfusate to levels approaching 100 fM via mechanisms that required extracellular Ca2+, 3) the dose-dependent increases in minute ventilation elicited by arterial injections of L-CSNO and L-GSNO were likely due to activation of small diameter unmyelinated C-fiber carotid body chemoafferents, 4) L-CSNO, but not L-GSNO, responses were markedly reduced in rats receiving continuous infusion (10 μmol/kg/min, IV) of both S-methyl-L-cysteine (L-SMC) and S-ethyl-L-cysteine (L-SEC), 5) ventilatory responses to hypoxic gas challenge (10% O2, 90% N2) were also due to the activation of small diameter unmyelinated C-fiber carotid body chemoafferents, and 6) the HVR was markedly diminished in rats receiving L-SMC plus L-SEC. This data provides evidence that rat PGCs synthesize an S-nitrosothiol with similar properties to L-CSNO that is released in an extracellular Ca2+-dependent manner by hypoxia.
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影响因子：
3.7
作者：
Gold, Olivia M. S.;Bardsley, Emma N. N.;Ponnampalam, Anna P. P.;Pauza, Audrys G. G.;Paton, Julian F. R.
通讯作者：
Paton, Julian F. R.
影响因子：
2.5
作者：
Atanasova, Dimitrinka Y.;Dimitrov, Nikolay D.;Lazarov, Nikolai E.
通讯作者：
Lazarov, Nikolai E.
影响因子：
4.9
作者：
Batenburg, Wendy W.;Kappers, Mariette H. W.;Danser, A. H. Jan
通讯作者：
Danser, A. H. Jan
影响因子：
5.5
作者：
Carpenter, E;Hatton, CJ;Peers, C
通讯作者：
Peers, C
DOI：
10.1007/0-387-31311-7_33
发表时间：
2006-01-01
期刊：
ARTERIAL CHEMORECEPTORS
影响因子：
--
作者：
Conde, SV;Caceres, AI;Gonzalez, C
通讯作者：
Gonzalez, C