Oxidised adenosine 5′-triphosphate, a P2X7 antagonist, is toxic to rat cerebellar granule neurones in vitro

Oxidised adenosine 5′-triphosphate, a P2X7 antagonist, is toxic to rat cerebellar granule neurones in vitro
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DOI:
10.1016/s0304-3940(01)02110-3
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发表时间:
2001-09-28
影响因子:
2.5
通讯作者:
Rothwell, NJ
Rothwell, NJ
中科院分区:
医学4区
文献类型:
--
作者:
Craighead, MW;Middlehurst, KML;Rothwell, NJ

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三磷酸腺苷(ATP)是中枢神经系统中的一种神经递质.细胞外ATP对许多细胞类型也是有毒的,例如通过其与P2 X膜受体,特别是P2 X(7)家族成员的相互作用。这些结果导致了一种假设,即ATP水平升高可能会加剧急性神经变性期间的损伤[4]。本研究的目的是研究ATP激动剂和拮抗剂对培养的大鼠小脑颗粒神经元的作用。无论是ATP,也不是P2 X激动剂苯甲酰苯甲酰-ATP(BzATP),是有毒的,当添加到初级神经元。然而,P2 X7拮抗剂氧化ATP(oATP)具有高度神经毒性。与BzATP共孵育可抑制该毒性。这些结果表明oATP是一种有效的神经毒素。(C)Elsevier Science爱尔兰有限公司出版。
Adenosine 5 ' -triphosphate (ATP) acts as a neurotransmitter in the central nervous system. Extracellular ATP is also toxic to a number of cell types e.g. via its interaction with P2X membrane receptors, specifically the P2X(7) family member. These results have led to the hypothesis that elevated ATP levels may exacerbate damage during acute neurodegeneration [4]. The aim of this study was to examine the effects of ATP agonists and antagonists on cultured rat cerebellar granule neurones. Neither ATP, nor the P2X agonist benzoylbenzoyl-ATP (BzATP), were toxic when added to primary neurones. However, the P2X7 antagonist, oxidised ATP (oATP) was highly neurotoxic. This toxicity was inhibited by coincubation with BzATP. These results demonstrate that oATP is a potent neurotoxin. (C) 2001 Published by Elsevier Science Ireland Ltd.