Transient adenosine signaling has been recently discovered in vivo, where the concentration is on average 180 nM and the duration only 3–4 s. In order to rapidly screen different brain regions and mechanisms of formation and regulation, here we develop a rat brain slice model to study adenosine transients. The frequency, concentration, and duration of transient adenosine events were compared in the prefrontal cortex (PFC), hippocampus (CA1), and thalamus. Adenosine transients in the PFC were similar to those in vivo, with a concentration of 160 ± 10 nM, and occurred frequently, averaging one every 50 ± 5 s. In the thalamus, transients were infrequent, occurring every 280 ± 40 s, and lower concentration (110 ± 10 nM), but lasted twice as long as in the PFC. In the hippocampus, adenosine transients were less frequent than those in the PFC, occurring every 79 ± 7 s, but the average concentration (240 ± 20 nM) was significantly higher. Adenosine transients are largely maintained after applying 200 nM tetrodotoxin, implying they are not activity dependent. The response to adenosine A₁ antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) differed by region; DPCPX had no significant effects in the PFC, but increased the average transient concentration in the thalamus and both the transient frequency and concentration in the hippocampus. Thus, the amount of adenosine available to activate receptors, and the ability to upregulate adenosine signaling with DPCPX, varies by brain region. This is an important consideration for designing treatments that modulate adenosine in order to cause neuroprotective effects.

中文翻译：

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脑切片中自发的，短暂的腺苷释放的区域变化

最近在体内发现了瞬时腺苷信号传导，其平均浓度为180 nM，持续时间仅为3-4 s。为了快速筛选不同的大脑区域以及形成和调节的机制，在这里我们开发了一个大鼠脑切片模型来研究腺苷瞬变。在前额叶皮层（PFC），海马（CA1）和丘脑中比较了短暂性腺苷事件的频率，浓度和持续时间。PFC中的腺苷瞬变类似于体内的瞬变，浓度为160±10 nM，并且频繁发生，平均每50±5 s发生一次。在丘脑中，不频繁发生瞬变，每280±40 s发生一次，且浓度较低（110±10 nM），但持续时间是PFC中的两倍。在海马中，腺苷瞬变的发生率低于PFC中的瞬变，每79±7 s发生一次，但平均浓度（240±20 nM）明显更高。施用200 nM河豚毒素后，腺苷瞬变现象得以很大程度上维持，这表明它们不是活性依赖性的。对腺苷A的反应_1个拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX）的区别在于区域；DPCPX对PFC没有明显影响，但增加了丘脑中的平均瞬时浓度以及海马中的瞬时频率和浓度。因此，可用于激活受体的腺苷的量以及用DPCPX上调腺苷信号传导的能力随大脑区域的不同而变化。这是设计调节腺苷以引起神经保护作用的治疗方法的重要考虑因素。