CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal.
FMUC - Faculty of Medicine, University of Coimbra, 3004-504, Coimbra, Portugal.
Purinergic Signal. 2024 Jun;20(3):247-255. doi: 10.1007/s11302-023-09937-y. Epub 2023 Mar 31.
The adenosine modulation system is mostly composed by inhibitory A receptors (AR) and the less abundant facilitatory A receptors (AR), the latter selectively engaged at high frequency stimulation associated with synaptic plasticity processes in the hippocampus. AR are activated by adenosine originated from extracellular ATP through ecto-5'-nucleotidase or CD73-mediated catabolism. Using hippocampal synaptosomes, we now investigated how adenosine receptors modulate the synaptic release of ATP. The AR agonist CGS21680 (10-100 nM) enhanced the K-evoked release of ATP, whereas both SCH58261 and the CD73 inhibitor α,β-methylene ADP (100 μM) decreased ATP release; all these effects were abolished in forebrain AR knockout mice. The AR agonist CPA (10-100 nM) inhibited ATP release, whereas the AR antagonist DPCPX (100 nM) was devoid of effects. The presence of SCH58261 potentiated CPA-mediated ATP release and uncovered a facilitatory effect of DPCPX. Overall, these findings indicate that ATP release is predominantly controlled by AR, which are involved in an apparent feedback loop of AR-mediated increased ATP release together with dampening of AR-mediated inhibition. This study is a tribute to María Teresa Miras-Portugal.
腺苷调节系统主要由抑制性 A 受体 (AR) 和较少的兴奋性 A 受体 (AR) 组成，后者在与海马突触可塑性过程相关的高频刺激下选择性地被激活。AR 通过细胞外 ATP 通过外核苷酸酶或 CD73 介导的代谢产生的腺苷激活。我们现在使用海马突触体研究了腺苷受体如何调节 ATP 的突触释放。AR 激动剂 CGS21680（10-100 nM）增强了 K 诱发的 ATP 释放，而 SCH58261 和 CD73 抑制剂 α,β-亚甲基 ADP（100 μM）均降低了 ATP 释放；所有这些作用在前脑 AR 敲除小鼠中均被消除。AR 激动剂 CPA（10-100 nM）抑制 ATP 释放，而 AR 拮抗剂 DPCPX（100 nM）则无作用。SCH58261 的存在增强了 CPA 介导的 ATP 释放，并揭示了 DPCPX 的促进作用。总体而言，这些发现表明 ATP 释放主要受 AR 控制，AR 参与了 AR 介导的增加的 ATP 释放的明显反馈回路，同时抑制了 AR 介导的抑制作用。本研究是对 María Teresa Miras-Portugal 的致敬。
