Decreases in rat brain aquaporin-4 expression following intracerebroventricular administration of an endothelin ETB receptor agonist
Decreases in rat brain aquaporin-4 expression following intracerebroventricular administration of an endothelin ETB receptor agonist
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DOI：
10.1016/j.neulet.2009.12.024
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发表时间：
2010-01
影响因子：
2.5
通讯作者：
Y. Koyama;Kazuhiro Tanaka
中科院分区：
文献类型：
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作者：
Y. Koyama;Kazuhiro Tanaka
水通道蛋白（Aquaporins，AQP）是一个水通道蛋白家族，其中一些在脑内表达。脑损伤后，如缺血和头部创伤，脑水通道蛋白的表达发生变化。然而，对脑AQP表达的调控知之甚少。内皮素（Endothelins，ET）是一种血管收缩肽，通过ET B受体调节受损神经组织的多种病理生理反应。为了显示ETB受体在脑AQP表达调节中的可能作用，在大鼠脑中检查了脑室内施用ETBagonist的作用。在大脑中，AQP 4 mRNA的拷贝数在AQP 1、3、4、5和9中最高。连续7天给予500 pmol/d的ET B选择性激动剂Ala 1，3，11，15-ET-1，可使大鼠大脑中AQP 4 mRNA水平降低，而对AQP 1，3，5和9 mRNA水平无影响。Ala 1，3，11，15-ET-1可降低脑组织AQP 4蛋白水平。免疫组化观察显示，Ala 1，3，11，15-ET-1灌注大鼠的GFAP阳性星形胶质细胞，而不是神经元，活化的小胶质细胞或脑毛细血管内皮细胞，具有免疫反应性的AQP 4。这些结果表明，脑ETB受体的激活导致AQP 4的表达减少，表明ET通过ETB受体下调脑AQP 4。
Aquaporins (AQPs) comprise a family of water channel proteins, some of which are expressed in brain. Expressions of brain AQPs are altered after brain insults, such as ischemia and head trauma. However, little is known about the regulation of brain AQP expression. Endothelins (ETs), vasoconstrictor peptides, regulate several pathophysiolgical responses of damaged nerve tissues via ETBreceptors. To show possible roles of ETBreceptors in the regulation of brain AQP expression, the effects of intracerebroventricular administration of an ETBagonist were examined in rat brain. In the cerebrum, the copy numbers of AQP4 mRNAs were highest among AQP1, 3, 4, 5 and 9. Continuous administration of 500pmol/day Ala1,3,11,15-ET-1, an ETBselective agonist, into rat brain for 7 days decreased the level of AQP4 mRNA in the cerebrum, but had no effect on AQP1, 3, 5 and 9 mRNA levels. The level of AQP4 protein in the cerebrum decreased by the administration of Ala1,3,11,15-ET-1. Immunohistochemical observations of Ala1,3,11,15-ET-1-infused rats showed that GFAP-positive astrocytes, but not neurons, activated microglia or brain capillary endothelial cells, had immunoreactivity for AQP4. These findings indicate that activation of brain ETBreceptors causes a decrease in AQP4 expression, suggesting that ET down-regulates brain AQP4 via ETBreceptors.