Functional Expression of Adenosine Receptors in Mesenchymal Stromal Cells

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 Ca²⁺ 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 Ca²⁺; Ca²⁺ responses to adenosine were generated according to the “all or nothing” principle: in small doses adenosine did not change the level of intracellular Ca²⁺, but it evoked Ca²⁺ 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 Ca²⁺ 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 IP₃; the latter activated IP₃ receptors and initiated the release of stored Ca²⁺, which most likely was dependent on the concentration of the agonist. This initial Ca²⁺ signal stimulated a large-scale release of Ca²⁺ from intracellular stores by the mechanism of Ca²⁺-induced Ca²⁺ release, which formed a secondary Ca²⁺ response of universal shape and amplitude.