Department of Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, 90134 Palermo, Italy.
Institut de Psychiatrie et Neurosciences de Paris, INSERM U1266, Université de Paris, F-75014 Paris, France.
Int J Mol Sci. 2020 Dec 5;21(23):9281. doi: 10.3390/ijms21239281.
Acute or chronic administration of guanosine (GUO) induces anxiolytic-like effects, for which the adenosine (ADO) system involvement has been postulated yet without a direct experimental evidence. Thus, we aimed to investigate whether adenosine receptors (ARs) are involved in the GUO-mediated anxiolytic-like effect, evaluated by three anxiety-related paradigms in rats. First, we confirmed that acute treatment with GUO exerts an anxiolytic-like effect. Subsequently, we investigated the effects of pretreatment with ADO or AR (CPA, CCPA) or AR (CGS21680) agonists 10 min prior to GUO on a GUO-induced anxiolytic-like effect. All the combined treatments blocked the GUO anxiolytic-like effect, whereas when administered alone, each compound was ineffective as compared to the control group. Interestingly, the pretreatment with nonselective antagonist caffeine or selective AR (DPCPX) or AR (ZM241385) antagonists did not modify the GUO-induced anxiolytic-like effect. Finally, binding assay performed in hippocampal membranes showed that [H]GUO binding became saturable at 100-300 nM, suggesting the existence of a putative GUO binding site. In competition experiments, ADO showed a potency order similar to GUO in displacing [H]GUO binding, whereas AR selective agonists, CPA and CGS21680, partially displaced [H]GUO binding, but the sum of the two effects was able to displace [H]GUO binding to the same extent of ADO alone. Overall, our results strengthen previous data supporting GUO-mediated anxiolytic-like effects, add new evidence that these effects are blocked by AR and AR agonists and pave, although they do not elucidate the mechanism of GUO and ADO receptor interaction, for a better characterization of GUO binding sites in ARs.
急性或慢性给予鸟苷（GUO）可诱导出焦虑样效应，这被认为与腺苷（ADO）系统有关，但尚无直接的实验证据。因此，我们旨在研究在大鼠的三种焦虑相关范式中，ADO 受体（ARs）是否参与了 GUO 介导的焦虑样效应。首先，我们证实急性给予 GUO 可产生焦虑样效应。随后，我们研究了在 GUO 给药前 10 分钟给予 ADO 或 AR（CPA、CCPA）或 AR（CGS21680）激动剂预处理对 GUO 诱导的焦虑样效应的影响。所有联合治疗均阻断了 GUO 的焦虑样效应，而单独给予每种化合物与对照组相比均无效。有趣的是，预先给予非选择性拮抗剂咖啡因或选择性 AR（DPCPX）或 AR（ZM241385）拮抗剂均不能改变 GUO 诱导的焦虑样效应。最后，在海马膜中进行的结合测定显示，[H]GUO 结合在 100-300 nM 处达到饱和，表明存在一个假定的 GUO 结合位点。在竞争实验中，ADO 在置换 [H]GUO 结合方面显示出与 GUO 相似的效力顺序，而 AR 选择性激动剂 CPA 和 CGS21680 部分置换 [H]GUO 结合，但两种效应的总和能够置换 [H]GUO 结合到与 ADO 单独相同的程度。总体而言，我们的结果加强了之前支持 GUO 介导的焦虑样效应的数据，并提供了新的证据，表明这些效应被 AR 和 AR 激动剂阻断，尽管它们没有阐明 GUO 和 ADO 受体相互作用的机制，但为更好地表征 AR 中的 GUO 结合位点铺平了道路。
Zotero 插件
