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.
Highlights
The review summarizes data evaluating the role of adenosine receptor signaling in murine hematopoietic functions
The aim of this review is to summarize the published data related to the effects of adenosine receptor signaling on various parameters of murine hematopoiesis, including quantitative indices of various compartments of the bone marrow, as well as the proliferation status and regeneration potential of hematopoietic cell populations investigated under conditions of the steady state, myelosuppression, and regeneration
Attention has been given to the problem of interactions of control mechanisms based on adenosine receptor signaling and action of hematopoietic cytokines
Summary
In 1929, Drury and Szent-Györgyi [1] described striking cardiovascular effects of adenosine injected into mammals. A naturally occurring nucleoside, is formed in the body by degradation of adenine nucleotides It can be formed intracellularly as well as extracellularly but acts in a regulatory sense only on extracellular receptors. The potency of adenosine receptor agonists is dependent on the type of the receptor activated and on the expression of the individual receptor subtypes which may be supposed to possess the ability to change in dependence on the functional state of the cell population investigated. It has to be taken into account that more adenosine receptor subtypes can be present on the same cell [7,8,9,10,11,12]. It has to be noted that the range of problems reviewed here does not include those dealing with adenosine receptor influence on functions of mature peripheral blood cells and on immune and inflammatory functions [13,14]
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