Nax signaling evoked by an increase in [Na+] in CSF induces water intake via EET-mediated TRPV4 activation.
Nax signaling evoked by an increase in [Na+] in CSF induces water intake via EET-mediated TRPV4 activation.
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CSF 中 [Na ] 增加引起的 Nax 信号通过 EET 介导的 TRPV4 激活诱导水摄入。
DOI：
10.1152/ajpregu.00352.2015
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
and Masaharu Noda
中科院分区：
文献类型：
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作者：
Sakuta Hiraki;Eri Nishihara;Takeshi Y. Hiyama;Chia-Hao Lin;and Masaharu Noda
水摄入行为是在感觉脑室周围器官（sCVOs）感知体液条件的大脑系统的控制下;然而，其潜在机制尚未详细阐明。Naxis是脑中钠（Na+）水平的传感器，并且已经提出瞬时受体电位香草酸（TRPV）通道TRPV 1和TRPV 4作为Na+传感器起作用。我们在此研究了TRPV 1-、TRPV 4-、Nax-和它们的双基因敲除（KO）小鼠脑室内注射高渗NaCl溶液后立即诱导的自发性饮水。TRPV 1-KO小鼠的水摄入量正常，而TRPV 4-KO和Nax-KO小鼠的水摄入量显著低于WT小鼠。Nax/TRPV 4-双KO小鼠的水摄入量与相应的单KO小鼠相似。当用特异性拮抗剂HC-067047阻断TRPV 4活性时，WT小鼠的饮水量显著减少，而TRPV 4-KO和Nax-KO小鼠的饮水量则没有减少。给予咪康唑也获得了类似的结果，咪康唑可抑制花生四烯酸（AA）生物合成环氧二十碳三烯酸（Epoxyeicosatrienoic acids，Epoxy），这是TRPV 4的内源性激动剂。侧脑室注射高渗NaCl和AA或5，6-EET使Nax-KO小鼠的饮水量恢复到野生型水平，但TRPV 4-KO小鼠的饮水量没有恢复。这些结果表明，Na+信号中产生的Na+阳性胶质细胞导致激活TRPV 4阳性神经元的sCVO刺激水的摄入，通过使用神经胶质细胞作为神经胶质递质。侧脑室注射等渗高渗山梨醇溶液诱导小，但显着的水摄入量同样在所有的基因型，这表明存在一个未知的传感器在大脑中。
Water-intake behavior is under the control of brain systems that sense body fluid conditions at sensory circumventricular organs (sCVOs); however, the underlying mechanisms have not yet been elucidated in detail. Naxis a sodium (Na+) level sensor in the brain, and the transient receptor potential vanilloid (TRPV) channels TRPV1 and TRPV4 have been proposed to function as osmosensors. We herein investigated voluntary water intake immediately induced after an intracerebroventricular administration of a hypertonic NaCl solution inTRPV1-,TRPV4-,Nax-, and their double-gene knockout (KO) mice. The induction of water intake byTRPV1-KO mice was normal, whereas intake byTRPV4-KO andNax-KO mice was significantly less than that by WT mice. Water intake byNax/TRPV4-double KO mice was similar to that by the respective single KO mice. When TRPV4 activity was blocked with a specific antagonist HC-067047, water intake by WT mice was significantly reduced, whereas intake byTRPV4-KO andNax-KO mice was not. Similar results were obtained with the administration of miconazole, which inhibits the biosynthesis of epoxyeicosatrienoic acids (EETs), endogenous agonists for TRPV4, from arachidonic acid (AA). Intracerebroventricular injection of hypertonic NaCl with AA or 5,6-EET restored water intake byNax-KO mice to the wild-type level but not that byTRPV4-KO mice. These results suggest that the Na+signal generated in Nax-positive glial cells leads to the activation of TRPV4-positive neurons in sCVOs to stimulate water intake by using EETs as gliotransmitters. Intracerebroventricular injection of equiosmolar hypertonic sorbitol solution induced small but significant water intake equally in all the genotypes, suggesting the presence of an unknown osmosensor in the brain.