Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus.
Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus.
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哺乳动物海马缺血期间 ATP 和腺苷释放的时间和机械解离。
DOI：
10.1111/j.1471-4159.2006.04425.x
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发表时间：
2007-06
影响因子：
4.7
通讯作者：
Dale N
中科院分区：
文献类型：
--
作者：
Frenguelli BG;Wigmore G;Llaudet E;Dale N
众所周知，腺苷在大脑代谢应激时释放，被认为具有神经保护作用。类似情况下的ATP释放研究要少得多。我们现在已经使用生物传感器来实时测量和比较在体外脑缺血期间海马片中ATP和腺苷的释放。ATP的释放只发生在缺氧去极化之后，而腺苷的释放几乎是在缺血发作后立即出现的。ATP的释放需要细胞外的钙离子。相反，细胞外钙离子的清除促进了腺苷的释放，而河豚毒素对ATP的释放和腺苷的释放都没有影响。阻断离子型谷氨酸受体可显著增加ATP的释放，但对腺苷的释放影响不大。缝隙连接半通道的抑制剂Carbenoxolone也能显著促进缺血的ATP释放，但对腺苷的释放影响不大。胞外ATPase抑制剂ARL 67156虽然略微增强了在缺血时检测到的三磷酸腺苷信号，但对腺苷的释放没有影响。用同型半胱氨酸硫内酯预处理可减少缺血时腺苷的释放，提示其来源于细胞内。腺苷转运抑制剂并没有抑制腺苷的释放，相反，它们使腺苷的释放增加了一倍。我们的数据表明，在缺血期间，ATP和腺苷的释放在很大程度上是独立的过程，具有不同的潜在机制。因此，这两种嘌呤对缺血脑中的神经元和神经胶质功能会产生不同的影响。
Adenosine is well known to be released during cerebral metabolic stress and is believed to be neuroprotective. ATP release under similar circumstances has been much less studied. We have now used biosensors to measure and compare in real time the release of ATP and adenosine during in vitro ischaemia in hippocampal slices. ATP release only occurred following the anoxic depolarisation, whereas adenosine release was apparent almost immediately after the onset of ischaemia. ATP release required extracellular Ca2+. By contrast adenosine release was enhanced by removal of extracellular Ca2+, whilst TTX had no effect on either ATP release or adenosine release. Blockade of ionotropic glutamate receptors substantially enhanced ATP release, but had only a modest effect on adenosine release. Carbenoxolone, an inhibitor of gap junction hemichannels, also greatly enhanced ischaemic ATP release, but had little effect on adenosine release. The ecto-ATPase inhibitor ARL 67156, whilst modestly enhancing the ATP signal detected during ischaemia, had no effect on adenosine release. Adenosine release during ischaemia was reduced by pre-treament with homosysteine thiolactone suggesting an intracellular origin. Adenosine transport inhibitors did not inhibit adenosine release, but instead they caused a twofold increase of release. Our data suggest that ATP and adenosine release during ischaemia are for the most part independent processes with distinct underlying mechanisms. These two purines will consequently confer temporally distinct influences on neuronal and glial function in the ischaemic brain.
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影响因子：
5.5
作者：
Dale, N;Pearson, T;Frenguelli, BG
通讯作者：
Frenguelli, BG
影响因子：
4.7
作者：
Gadalla, AE;Pearson, T;Frenguelli, BG
通讯作者：
Frenguelli, BG
影响因子：
5.3
作者：
Gourine, AV;Llaudet, E;Spyer, KM
通讯作者：
Spyer, KM
影响因子：
--
作者：
Contreras, JE;Sánchez, HA;Sáez, JC
通讯作者：
Sáez, JC
影响因子：
3.5
作者：
Cunha, Rodrigo A
通讯作者：
Cunha, Rodrigo A