The Role of Adenosine Receptor Agonists in Regulation of Hematopoiesis

Abstract: The review summarizes data evaluating the role of adenosine receptor signaling in murine hematopoietic functions. The studies carried out utilized either non-selective activation of adenosine receptors induced by elevation of extracellular adenosine or by administration of synthetic adenosine analogs having various proportions of selectivity for a particular receptor. Numerous studies have described stimulatory effects of non-selective activation of adenosine receptors, manifested as enhancement of proliferation of cells at various levels of the hematopoietic hierarchy. Subsequent experimental approaches, considering the hematopoiesis-modulating action of adenosine receptor agonists with a high level of selectivity to individual adenosine receptor subtypes, have revealed differential effects of various adenosine analogs. Whereas selective activation of A₁ receptors has resulted in suppression of proliferation of hematopoietic progenitor and precursor cells, that of A₃ receptors has led to stimulated cell proliferation in these cell compartments. Thus, A₁ and A₃ receptors have been found to play a homeostatic role in suppressed and regenerating hematopoiesis. Selective activation of adenosine A₃ receptors has been found to act curatively under conditions of drug- and radiation-induced myelosuppression. The findings in these and further research areas will be summarized and mechanisms of hematopoiesis-modulating action of adenosine receptor agonists will be discussed.