Glial cell‐derived glutamate mediates autocrine cell volume regulation in the retina: activation by VEGF

Glial cell‐derived glutamate mediates autocrine cell volume regulation in the retina: activation by VEGF
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胶质细胞衍生的谷氨酸介导视网膜自分泌细胞体积调节:VEGF 的激活

DOI:
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发表时间:
2007
影响因子:
4.7
通讯作者:
A. Bringmann
A. Bringmann
中科院分区:
医学2区
文献类型:
--
作者:
A. Wurm;T. Pannicke;P. Wiedemann;A. Reichenbach;A. Bringmann

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星形胶质细胞是谷氨酸和ATP等胶质递质的来源。我们在这里证明,胶质递质具有自分泌功能的调节细胞体积。在存在炎症介质或氧化应激的情况下,以及在钾通道阻断或下调期间,低渗应激诱导视网膜神经胶质细胞肿胀。血管内皮生长因子抑制视网膜切片或分离细胞中胶质细胞的渗透性肿胀。这种作用是由激酶结构域区域/flk-1受体诱导的钙依赖性谷氨酸从神经胶质细胞释放介导的,随后刺激神经胶质I/II组代谢型谷氨酸受体。激酶结构域区域/flk-1或谷氨酸受体的激活诱发了钙非依赖性的自分泌肿胀抑制性嘌呤能信号级联。该级联反应涉及ATP和腺苷的释放,以及嘌呤能P2 Y1和腺苷A1受体的激活,导致钾和氯通道的开放和细胞肿胀的抑制。神经胶质细胞体积的多巴胺能-嘌呤能调节可能在强烈神经元激活期间细胞外空间体积的稳态中具有重要功能,这与视网膜中神经元细胞结构的肿胀有关。然而,神经胶质细胞衍生的谷氨酸也可能有助于活化神经元的肿胀,因为碘乙酸盐对神经胶质细胞的代谢中毒抑制了由离子型谷氨酸受体活化介导的神经元细胞肿胀。
Astroglial cells are a source for gliotransmitters such as glutamate and ATP. We demonstrate here that gliotransmitters have autocrine functions in the regulation of cellular volume. Hypoosmotic stress in the presence of inflammatory mediators or oxidative stress, and during blockade or down‐regulation of potassium channels, induces swelling of retinal glial cells. Vascular endothelial growth factor inhibits the osmotic swelling of glial cells in retinal slices or isolated cells. This effect was mediated by a kinase domain region/flk‐1 receptor‐evoked calcium dependent release of glutamate from glial cells, and subsequent stimulation of glial group I/II metabotropic glutamate receptors. Activation of kinase domain region/flk‐1 or glutamate receptors evoked an autocrine swelling‐inhibitory purinergic signaling cascade that was calcium‐independent. This cascade involved the release of ATP and adenosine, and the activation of purinergic P2Y1 and adenosine A1 receptors, resulting in the opening of potassium and chloride channels and inhibition of cellular swelling. The glutamatergic‐purinergic regulation of the glial cell volume may be functionally important in the homeostasis of the extracellular space volume during intense neuronal activation which is associated with a swelling of neuronal cell structures in the retina. However, glial cell‐derived glutamate may also contribute to the swelling of activated neurons since metabolic poisoning of glial cells by iodoacetate inhibits the neuronal cell swelling mediated by activation of ionotropic glutamate receptors.
DOI: 10.3171/jns.1995.83.6.1051
发表时间: 1995-12-01
影响因子: 4.1
作者:
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通讯作者: KIMELBERG, HK
DOI: 10.1016/j.paid.2017.01.013
发表时间: 2017-05-01
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