Department of Chemistry, University of Virginia, Charlottesville, Virginia, United States of America.
PLoS One. 2014 Jan 29;9(1):e87165. doi: 10.1371/journal.pone.0087165. eCollection 2014.
Adenosine is a neuroprotective agent that inhibits neuronal activity and modulates neurotransmission. Previous research has shown adenosine gradually accumulates during pathologies such as stroke and regulates neurotransmission on the minute-to-hour time scale. Our lab developed a method using carbon-fiber microelectrodes to directly measure adenosine changes on a sub-second time scale with fast-scan cyclic voltammetry (FSCV). Recently, adenosine release lasting a couple of seconds has been found in murine spinal cord slices. In this study, we characterized spontaneous, transient adenosine release in vivo, in the caudate-putamen and prefrontal cortex of anesthetized rats. The average concentration of adenosine release was 0.17±0.01 µM in the caudate and 0.19±0.01 µM in the prefrontal cortex, although the range was large, from 0.04 to 3.2 µM. The average duration of spontaneous adenosine release was 2.9±0.1 seconds and 2.8±0.1 seconds in the caudate and prefrontal cortex, respectively. The concentration and number of transients detected do not change over a four hour period, suggesting spontaneous events are not caused by electrode implantation. The frequency of adenosine transients was higher in the prefrontal cortex than the caudate-putamen and was modulated by A1 receptors. The A1 antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine, 6 mg/kg i.p.) increased the frequency of spontaneous adenosine release, while the A1 agonist CPA (N(6)-cyclopentyladenosine, 1 mg/kg i.p.) decreased the frequency. These findings are a paradigm shift for understanding the time course of adenosine signaling, demonstrating that there is a rapid mode of adenosine signaling that could cause transient, local neuromodulation.
腺苷是一种神经保护剂，可抑制神经元活动并调节神经递质传递。先前的研究表明，腺苷在中风等病理过程中逐渐积累，并在分钟到小时的时间尺度上调节神经递质传递。我们实验室开发了一种使用碳纤维微电极的方法，通过快速扫描循环伏安法（FSCV）在亚秒级时间尺度上直接测量腺苷的变化。最近，在小鼠脊髓切片中发现了持续几秒钟的腺苷释放。在这项研究中，我们在麻醉大鼠的尾壳核和前额叶皮层中对自发的、短暂的腺苷释放进行了特征描述。尾壳核中腺苷释放的平均浓度为 0.17±0.01µM，前额叶皮层中为 0.19±0.01µM，尽管范围很大，从 0.04 到 3.2µM。自发腺苷释放的平均持续时间分别为尾壳核 2.9±0.1 秒和前额叶皮层 2.8±0.1 秒。在四个小时的时间内，检测到的自发事件的浓度和数量没有变化，这表明自发事件不是由电极植入引起的。前额叶皮层中腺苷瞬变的频率高于尾壳核，并且可以被 A1 受体调节。A1 拮抗剂 DPCPX（8-环戊基-1,3-二丙基黄嘌呤，6mg/kg i.p.）增加了自发腺苷释放的频率，而 A1 激动剂 CPA（N6-环戊基腺苷，1mg/kg i.p.）降低了频率。这些发现是理解腺苷信号时间过程的范式转变，表明存在一种快速的腺苷信号模式，可能导致短暂的局部神经调节。
