Elevated pressure triggers a physiological release of ATP from the retina: Possible role for pannexin hemichannels.
Elevated pressure triggers a physiological release of ATP from the retina: Possible role for pannexin hemichannels.
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DOI：
10.1016/j.neuroscience.2008.08.036
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发表时间：
2008-11-19
期刊：
影响因子：
3.3
通讯作者：
Mitchell CH
中科院分区：
文献类型：
--
作者：
Reigada D;Lu W;Zhang M;Mitchell CH
尽管压力与神经化学失衡或细胞损伤之间的联系机制尚未完全建立，但增加的静水压力会损害神经元。在整个身体中，剪切力、细胞伸展或压力变化等机械扰动都会导致ATP的过量释放。因此，神经组织压力的增加可能会触发ATP释放到细胞外空间的增加。当刺激视网膜神经节细胞上的ATP的P2X7受体导致细胞内钙升高和兴奋性死亡时，我们询问细胞外ATP水平的增加是否伴随着整个视网膜压力的升高。增加牛视网膜周围的静水压力，并测定邻近视网膜的玻璃体组织中的ATP含量。每增加20毫米汞柱，玻璃体内的三磷酸腺苷浓度就会增加三倍。在20-100 mm Hg范围内，三磷酸腺苷水平与压力升高程度密切相关。这种增加在较低压力下是暂时的，但在较高压力下会持续。无论是使用氮气还是空气来增加压力，玻璃体ATP的上升都是相同的，这意味着氧分压的变化没有贡献。乳酸脱氢酶活性不受压力的影响，排除了细胞裂解的实质性贡献。5-硝基-2-(3-苯丙氨基)苯甲酸(NPPB)或甘草酸(CBX)可显著抑制ATP的升高。虽然这与通过膜联蛋白半通道的生理释放ATP是一致的，但不能排除阴离子通道、囊泡释放或其他机制的贡献。总而言之，压力的阶梯升高会导致细胞外ATP沐浴视网膜神经元的水平生理性增加。这种细胞外过量的三磷酸腺苷可能与急性青光眼中神经节细胞的死亡有关，并提示三磷酸腺苷在伴随颅内压升高而引起的神经元损伤中发挥了作用。
Increased hydrostatic pressure can damage neurons, although the mechanisms linking pressure to neurochemical imbalance or cell injury are not fully established. Throughout the body, mechanical perturbations such as shear stress, cell stretching, or changes in pressure can lead to excessive release of ATP. It is thus possible that increased pressure across neural tissues triggers an elevated release of ATP into extracellular space. As stimulation of the P2X7 receptor for ATP on retinal ganglion cells leads to elevation of intracellular calcium and excitotoxic death, we asked whether increased levels of extracellular ATP accompanied an elevation in pressure across the retina. The hydrostatic pressure surrounding bovine retinal eyecups was increased and the ATP content of the vitreal compartment adjacent to the retina was determined. A step increase of only 20 mmHg induced a three-fold increase in the vitreal ATP concentration. The ATP levels correlated closely with the degree of pressure increase over 20–100 mmHg range. The increase was transient at lower pressures but sustained at higher pressures. The rise in vitreal ATP was the same regardless of whether nitrogen or air was used to increase pressure, implying changes in oxygen partial pressure did not contribute. Lactate dehydrogenase activity was not affected by pressure, ruling out a substantial contribution from cell lysis. The ATP increase was largely inhibited by either 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) or carbenoxolone (CBX). While this is consistent with physiological release of ATP through pannexins hemichannels, a contribution from anion channels, vesicular release or other mechanisms cannot be ruled out. In conclusion, a step elevation in pressure leads to a physiologic increase in the levels of extracellular ATP bathing retinal neurons. This excess extracellular ATP may link increased pressure to the death of ganglion cells in acute glaucoma, and suggests a role for ATP in the neuronal damage accompanying increased intracranial pressure.
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DOI：
10.1016/j.bbrc.2004.07.081
发表时间：
2004-09-10
影响因子：
3.1
作者：
Buttigieg, J;Nurse, CA
通讯作者：
Nurse, CA
体积调节的阴离子通道是主动脉内皮细胞中的自动/旁分泌核苷酸释放途径。
影响因子：
3.8
作者：
Hisadome, Kazunari;Koyama, Tetsuya;Kimura, Chiwaka;Droogmans, Guy;Ito, Yushi;Oike, Masahiro
通讯作者：
Oike, Masahiro
影响因子：
5.5
作者：
Ferguson, DR;Kennedy, I;Burton, TJ
通讯作者：
Burton, TJ
影响因子：
4.8
作者：
Buyse, G;Voets, T;Eggermont, J
通讯作者：
Eggermont, J
影响因子：
25
作者：
Davalos, D;Grutzendler, J;Gan, WB
通讯作者：
Gan, WB