Functional Expression of Adenosine Receptors in Mesenchymal Stromal Cells

摘要

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.