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Functional Expression of Adenosine Receptors in Mesenchymal Stromal Cells
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology ( IF 1.1 ) Pub Date : 2020-10-01 , DOI: 10.1134/s1990747820030101
E. N. Kochkina , A. P. Cherkashin , N. V. Kabanova , E. A. Sokolova , M. F. Bystrova , P. D. Kotova

Abstract Extracellular adenosine is a signaling molecule involved in the regulation of physiological processes in a variety of cells, including mesenchymal stromal cells (MSCs). We have shown using microphotometry and Ca 2+ probes that the population of MSCs isolated from human adipose tissue contained a small (5–10%) subpopulation of adenosinergic cells. In these cells, A1, A2A, and A2B adenosine receptors functioned; they were coupled with a phosphoinositide signaling cascade. Stimulation of adenosinergic MSCs by adenosine initiated the mobilization of intracellular Ca 2+ ; Ca 2+ responses to adenosine were generated according to the “all or nothing” principle: in small doses adenosine did not change the level of intracellular Ca 2+ , but it evoked Ca 2+ responses of almost identical shape and amplitude at any concentration exceeding a threshold. It is noteworthy that the duration of the response delay from the moment of application of adenosine decreased as its concentration increased. Key stages of the generation of the Ca 2+ response to adenosine were studied using the inhibitor analysis. The obtained data indicated that the adenosine receptor activated phospholipase C, which stimulated the production of IP 3 ; the latter activated IP 3 receptors and initiated the release of stored Ca 2+ , which most likely was dependent on the concentration of the agonist. This initial Ca 2+ signal stimulated a large-scale release of Ca 2+ from intracellular stores by the mechanism of Ca 2+ -induced Ca 2+ release, which formed a secondary Ca 2+ response of universal shape and amplitude.

中文翻译:

腺苷受体在间充质基质细胞中的功能表达

摘要 细胞外腺苷是一种信号分子,参与调节包括间充质基质细胞 (MSCs) 在内的多种细胞的生理过程。我们已经使用显微光度法和 Ca 2+ 探针表明,从人类脂肪组织中分离出的 MSC 群体包含少量(5-10%)腺苷能细胞亚群。在这些细胞中,A1、A2A 和 A2B 腺苷受体起作用;它们与磷酸肌醇信号级联反应相结合。腺苷对腺苷能 MSCs 的刺激引发细胞内 Ca 2+ 的动员;Ca 2+ 对腺苷的反应是根据“全有或全无”原则产生的:小剂量的腺苷不会改变细胞内 Ca 2+ 的水平,但在任何浓度超过一个门槛。值得注意的是,从应用腺苷的那一刻起,反应延迟的持续时间随着其浓度的增加而减少。使用抑制剂分析研究了产生对腺苷的 Ca 2+ 响应的关键阶段。得到的数据表明,腺苷受体激活了磷脂酶C,从而刺激了IP 3 的产生;后者激活 IP 3 受体并启动储存的 Ca 2+ 的释放,这很可能取决于激动剂的浓度。该初始Ca 2+ 信号通过Ca 2+ 诱导Ca 2+ 释放的机制刺激细胞内储存的Ca 2+ 大规模释放,形成具有普遍形状和幅度的次级Ca 2+ 响应。
更新日期:2020-10-01
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