pH and proton-sensitive receptors in brain ischemia.
pH and proton-sensitive receptors in brain ischemia.
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DOI：
10.1177/0271678x221089074
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发表时间：
2022-08
影响因子：
6.3
通讯作者：
Simon, Roger P.
中科院分区：
文献类型：
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作者：
Zha, Xiang-ming;Xiong, Zhi-Gang;Simon, Roger P.
pH = 7.4时，胞外质子浓度为40 nM。在脑缺血等疾病情况下，质子浓度可达µM范围。为了应对细胞外质子浓度的增加，哺乳动物的大脑至少表达了三类质子受体。酸感离子通道（asic）是神经元中主要的阳离子质子受体。质子激活的氯离子通道（PAC），也被称为酸敏向外整流阴离子通道（ASOR; TMEM206），介导酸诱导的氯离子电流。除了质子激活通道外，GPR4、GPR65（又名TDAG8， t细胞死亡相关基因8）和GPR68（又名OGR1，卵巢癌G蛋白偶联受体1）也是质子敏感的G蛋白偶联受体（gpcr）。虽然早期对这些gpcr的研究主要集中在外周细胞，但我们和其他人最近提供了证据，证明它们在脑损伤中的功能重要性。具体来说，GPR4在脑内皮中表达强烈，GPR65在一小部分小胶质细胞中表达，而GPR68在脑神经元中主要表达。在这里，为了更好地了解脑酸信号及其在缺血性损伤中的作用，我们将回顾最近关于质子敏感gpcr在酸中毒和脑缺血后脑血管功能、神经炎症和神经元损伤中的差异作用的研究结果。
Extracellular proton concentration is at 40 nM when pH is 7.4. In disease conditions such as brain ischemia, proton concentration can reach µM range. To respond to this increase in extracellular proton concentration, the mammalian brain expresses at least three classes of proton receptors. Acid-sensing ion channels (ASICs) are the main neuronal cationic proton receptor. The proton-activated chloride channel (PAC), which is also known as (aka) acid-sensitive outwardly rectifying anion channel (ASOR; TMEM206), mediates acid-induced chloride currents. Besides proton-activated channels, GPR4, GPR65 (aka TDAG8, T-cell death-associated gene 8), and GPR68 (aka OGR1, ovarian cancer G protein-coupled receptor 1) function as proton-sensitive G protein-coupled receptors (GPCRs). Though earlier studies on these GPCRs mainly focus on peripheral cells, we and others have recently provided evidence for their functional importance in brain injury. Specifically, GPR4 shows strong expression in brain endothelium, GPR65 is present in a fraction of microglia, while GPR68 exhibits predominant expression in brain neurons. Here, to get a better view of brain acid signaling and its contribution to ischemic injury, we will review the recent findings regarding the differential contribution of proton-sensitive GPCRs to cerebrovascular function, neuroinflammation, and neuronal injury following acidosis and brain ischemia.
DOI：
10.1038/jcbfm.2008.145
发表时间：
2009-03
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
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