Angiotensin-(1-7) inhibits neuronal activity of dorsolateral periaqueductal gray via a nitric oxide pathway.
Angiotensin-(1-7) inhibits neuronal activity of dorsolateral periaqueductal gray via a nitric oxide pathway.
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DOI：
10.1016/j.neulet.2012.06.031
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发表时间：
2012-08-01
影响因子：
2.5
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Xing J;Kong J;Lu J;Li J
中脑导水管周围灰质（PAG）是一个与心血管调节、疼痛调节和行为反应有关的生理功能的神经部位。近年来，血管紧张素-(1-7)[Ang-(1-7)]被认为是中枢神经系统肾素-血管紧张素系统的重要生物活性成分。本研究的目的是确定1)在背外侧PAG （dl-PAG）内存在Ang-(1-7)受体Mas-R， 2) Ang-(1-7)在调节dl-PAG神经元活性中的作用，以及3)Ang-(1-7)发挥调节作用的机制。Western blot分析显示，Mas-R出现在dl-PAG中。全细胞膜片钳记录显示，100 nM的Ang-(1-7)使dl-PAG神经元放电速率从对照组的4.35±0.32 Hz降低到1.06±0.34 Hz （P<0.05，与对照组相比）。经Mas-R抑制剂a -779预处理，Ang-输注时放电速率为4.66±0.62 Hz （P < 0.05，与对照组相比）（1-7）。此外，神经元一氧化氮合酶（nNOS）在三种亚型中主要定位于dl-PAG内。ng-(1-7)对PAG神经元活性的影响在nNOS抑制剂S-methyl-L-thiocitrulline （SMTC）存在下减弱。Ang-(1-7)配合SMTC预处理时，放电率分别为4.21±0.39 Hz和4.09±0.47 Hz （P < 0.05）。这些发现表明Ang-(1-7)通过NO依赖的信号通路对dl-PAG起抑制作用。这为Ang-(1-7)和Mas R在中枢神经系统中调节各种功能的生理作用提供了基础。
The midbrain periaqueductal gray (PAG) is a neural site for several physiological functions related to cardiovascular regulation, pain modulation and behavioral reactions. Recently, angiotensin-(1-7) [Ang-(1-7)] has been considered as an important biologically active component of the renin-angiotensin system in the CNS. The purpose of this study was to determine 1) existence of Ang-(1-7) receptor, Mas-R, within the dorsolateral PAG (dl-PAG), 2) the role for Ang-(1-7) in modulating activity of dl-PAG neurons, and 3) the mechanisms by which Ang-(1-7) plays a regulatory role. Western blot analysis showed that Mas-R appears within the dl-PAG. Whole cell patch-clamp recording demonstrated that the discharge rates of dl-PAG neurons were decreased from 4.35±0.32 Hz of control to 1.06±0.34 Hz (P<0.05, vs. control) by 100 nM of Ang-(1-7). With pretreatment of A-779, a Mas-R inhibitor, the discharge rate was 4.66±0.62 Hz (P > 0.05, vs. control) during infusion of Ang-(1-7). Additionally, neuronal nitric oxide synthase (nNOS) was largely localized within the dl-PAG among the three isoforms. The effects of Ang-(1-7) on neuronal activity of the PAG were attenuated in the presence of S-methyl-L-thiocitrulline (SMTC), a nNOS inhibitor. The discharge rates were 4.21±0.39 Hz in control and 4.09±0.47 Hz (P > 0.05, vs. control) when Ang-(1-7) was applied with pretreatment of SMTC. Those findings suggest that Ang-(1-7) plays an inhibitory role in the dl-PAG via a NO dependent signaling pathway. This offers the basis for the physiological role of Ang-(1-7) and Mas R in the regulation of various functions in the CNS.
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影响因子：
6.1
作者：
DAmico, M;DiFilippo, C;Rossi, F
通讯作者：
Rossi, F
DOI：
10.1111/j.1600-0773.1992.tb01618.x
发表时间：
1992-06-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
STECKELINGS, UM;OBERMULLER, N;UNGER, T
通讯作者：
UNGER, T
影响因子：
2.9
作者：
Lu, Jian;Xing, Jihong;Li, Jianhua
通讯作者：
Li, Jianhua
影响因子：
2.5
作者：
McGaraughty, S;Chu, KL;Jarvis, MF
通讯作者：
Jarvis, MF
DOI：
10.1073/pnas.1432869100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Santos, RAS;Silva, ACSE;Walther, T
通讯作者：
Walther, T