Adenosine Release Evoked by Short Electrical Stimulations in Striatal Brain Slices is Primarily Activity Dependent.
Adenosine Release Evoked by Short Electrical Stimulations in Striatal Brain Slices is Primarily Activity Dependent.
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DOI：
10.1021/cn100037d
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发表时间：
2010-10-01
影响因子：
5
通讯作者：
Venton, B. Jill
中科院分区：
文献类型：
--
作者：
Pajski, Megan L.;Venton, B. Jill
关键词：
腺苷是大脑中重要的神经调节剂。传统上，腺苷被认为是通过细胞外机制（通过释放的 ATP 分解在细胞外形成）或细胞内机制（将细胞内产生的腺苷转运出去）在细胞外空间中产生的。最近，还提出了活性依赖性腺苷释放的第三种机制。在这里，我们使用快速扫描循环伏安法来比较纹状体大鼠脑切片中低频或高频刺激引起的腺苷形成的时间过程和机制。低频刺激（10 Hz 5 个脉冲）导致平均腺苷流出量为 0.22 ± 0.02 μM，而高频刺激（5 个脉冲，60 Hz）引起 0.36 ± 0.04 μM。通过用 S-(4-硝基苯甲基)-6-硫代肌苷 (NBTI) 或丙戊茶碱抑制腺苷转运蛋白来阻断细胞内形成，不会减少任一频率的释放，表明释放不是由于细胞内机制所致。使用 ARL-67156 阻断细胞外形成可减少约 60% 的低频释放，但不影响高频释放。低频和高频刺激释放几乎完全被钙的去除所阻断，表明活性依赖性。减少多巴胺流出不会影响腺苷释放，但抑制离子型谷氨酸受体会影响腺苷释放，表明腺苷释放依赖于谷氨酸的下游效应。因此，短时、高频的生理刺激后腺苷的释放与转运蛋白活性或ATP代谢无关，可能是由于谷氨酸受体激活后腺苷的直接释放所致。
Adenosine is an important neuromodulator in the brain. Traditionally, adenosine is thought to arise in the extracellular space by either an extracellular mechanism, where it is formed outside the cell by the breakdown of released ATP, or an intracellular mechanism, where adenosine made inside the cell is transported out. Recently, a proposed third mechanism of activity dependent adenosine release has also been proposed. Here, we used fast-scan cyclic voltammetry to compare the time course and mechanism of adenosine formation evoked by either low- or high-frequency stimulations in striatal rat brain slices. Low-frequency stimulations (5 pulses at 10 Hz) resulted in an average adenosine efflux of 0.22 ± 0.02 μM, while high-frequency stimulations (5 pulses, 60 Hz) evoked 0.36 ± 0.04 μM. Blocking intracellular formation by inhibiting adenosine transporters with S-(4-nitrobenzyl)-6-thioinosine (NBTI) or propentofylline did not decrease release for either frequency, indicating that the release was not due to the intracellular mechanism. Blocking extracellular formation with ARL-67156 reduced low-frequency release about 60%, but did not affect high-frequency release. Both low- and high-frequency stimulated release were almost completely blocked by removal of calcium, indicating activity dependence. Reducing dopamine efflux did not affect adenosine release but inhibiting ionotropic glutamate receptors did, indicating that adenosine release is dependent on downstream effects of glutamate. Therefore, adenosine release after short, high-frequency physiological stimulations is independent of transporter activity or ATP metabolism, and may be due to direct release of adenosine after glutamate receptor activation.
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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。
影响因子：
4.7
作者：
Frenguelli BG;Wigmore G;Llaudet E;Dale N
通讯作者：
Dale N
DOI：
10.1016/s0169-328x(96)00244-6
发表时间：
1996-12-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Anderson, CM;Xiong, W;Parkinson, FE
通讯作者：
Parkinson, FE
影响因子：
4.2
作者：
Heien, MLAV;Phillips, PEM;Wightman, RM
通讯作者：
Wightman, RM
影响因子：
3
作者：
JONES, SR;MICKELSON, GE;WIGHTMAN, RM
通讯作者：
WIGHTMAN, RM
影响因子：
2.9
作者：
Koos, BJ;Kruger, L;Murray, TF
通讯作者：
Murray, TF