Speth Robert C, Karamyan Vardan T
Department of Pharmacology, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, Oxford, MS 38677, USA.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):283-93. doi: 10.1007/s00210-007-0238-7. Epub 2008 Jan 3.
This review addresses classical and novel aspects of the brain angiotensin system. The brain contains both the AT1 and AT2 angiotensin II (Ang II) receptor subtypes which are well-characterized guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs). Like other GPCRs, novel signal transduction pathways and protein interactions are being described for Ang II receptors. For brain AT1 receptors, there is a controversy regarding the identity of the active angiotensin peptide in the brain which is addressed in this review. This review also summarizes a recent discovery of a novel, membrane-bound, non-AT1, non-AT2 binding site for angiotensin peptides that appears to be brain-specific. This binding site is unmasked by a limited concentration range of the organometallic sulfhydryl-reactive agent p-chloromercuribenzoic acid (PCMB) suggesting that functional expression of this binding site may depend on the redox state of the milieu of the brain. While this binding site has similarities to a previously described soluble angiotensin-binding protein found in liver that is unmasked by PCMB, it has many different characteristics. The possible functional significance of this novel non-AT1, non-AT2 binding site for angiotensin peptides as a mediator of non-traditional actions of Ang II in the brain, e.g., stimulation of dopamine release from the striatum, as a peptidase, or as a clearance receptor, and the importance of the state of the internal environment of the brain to its function is reviewed.
本综述探讨了脑内血管紧张素系统的经典及新发现方面。脑内同时存在血管紧张素 II（Ang II）的 AT1 和 AT2 受体亚型，它们是特征明确的鸟嘌呤核苷酸结合蛋白（G 蛋白）偶联受体（GPCR）。与其他 GPCR 一样，目前正在描述 Ang II 受体的新信号转导途径和蛋白质相互作用。对于脑内 AT1 受体，本综述探讨了关于脑内活性血管紧张素肽身份的争议。本综述还总结了最近发现的一种新的、膜结合的、非 AT1 非 AT2 的血管紧张素肽结合位点，该位点似乎具有脑特异性。该结合位点可被有机金属巯基反应剂对氯汞苯甲酸（PCMB）的有限浓度范围暴露，这表明该结合位点的功能表达可能取决于脑内环境的氧化还原状态。虽然该结合位点与先前在肝脏中发现的可被 PCMB 暴露的可溶性血管紧张素结合蛋白有相似之处，但它有许多不同的特征。本文综述了这种新的非 AT1 非 AT2 血管紧张素肽结合位点作为 Ang II 在脑内非传统作用（如刺激纹状体释放多巴胺）的介质、作为肽酶或作为清除受体的可能功能意义，以及脑内环境状态对其功能的重要性。
