Regaya Imed, Aidi-Knani Sabrine, By Youlet, Condo Jocelyne, Gerolami Victoria, Berge-Lefranc Jean-Louis, Ben Hamida Jeannette, Sabatier Jean-Marc, Fenouillet Emmanuel, Guieu Régis, Ruf Jean
Unit of Functional Proteomics and Organic Food Preservation, Higher Institute of Applied Biological Sciences of Tunis, University of Tunis El Manar , Tunis, Tunisia . ; Higher Institute of Environmental Sciences and Technologies, University of Carthage , Carthage, Tunisia .
Biores Open Access. 2013 Apr;2(2):163-8. doi: 10.1089/biores.2012.0282.
Adenosine is a nucleoside displaying various biological effects via stimulation of four G-protein-coupled receptors, A1, A2A, A2B, and A3. Adenosine also modulates voltage-gated (Kv) and small conductance calcium-activated (SKCa) potassium channels. The effect of these potassium channels on the expression of adenosine receptors is poorly understood. We evaluated the action of BgK (a natural Kv channel blocker) and Lei-Dab7 (a synthetic SKCa channel blocker) on the expression of adenosine A2A receptors (A2AR) in Jurkat human T cells. We found that Lei-Dab7, but not BgK, increased the maximal binding value of the tritiated ligand ZM241385 to A2AR in a dose-dependent manner (+45% at 5 nM; +70% at 50 nM as compared to control). These results were further confirmed by Western blotting using a specific monoclonal antibody to human A2AR. The ligand affinity-related dissociation constant and A2AR mRNA amount were not significantly modified by either drug. We suggest that modulation of SKCa channels can influence membrane expression of A2AR and thus has a therapeutic potential.
腺苷是一种核苷，它通过刺激四种G蛋白偶联受体A1、A2A、A2B和A3发挥多种生物学效应。腺苷还可调节电压门控钾通道（Kv）和小电导钙激活钾通道（SKCa）。这些钾通道对腺苷受体表达的影响尚不清楚。我们评估了BgK（一种天然的Kv通道阻滞剂）和Lei-Dab7（一种合成的SKCa通道阻滞剂）对Jurkat人T细胞中腺苷A2A受体（A2AR）表达的作用。我们发现，Lei-Dab7而非BgK，以剂量依赖性方式增加了氚化配体ZM241385与A2AR的最大结合值（与对照组相比，5 nM时增加45%；50 nM时增加70%）。使用针对人A2AR的特异性单克隆抗体进行的蛋白质印迹法进一步证实了这些结果。两种药物均未显著改变配体亲和力相关的解离常数和A2AR mRNA的量。我们认为，对SKCa通道的调节可影响A2AR的膜表达，因此具有治疗潜力。
