There exists a requirement for drugs which would be useful in therapy of an acute radiation damage of a mammalian organism. The aim of the study was to evaluate survival parameters in mice exposed to a lethal γ-ray dose of 8.5 Gy and treated with single doses of an adenosine A(3) receptor agonist, IB-MECA, or a cyclooxygenase-2 (COX-2) inhibitor, meloxicam, administered alone or in a combination early after irradiation, i.e., 0.5 and 1 h post-irradiation, respectively. The assessed parameters were the mean survival time (MST) and the cumulative percentage 30-day survival (CPS). Administrations of single intraperitoneal doses of either IB-MECA 0.5 h post-irradiation or meloxicam 1 h post-irradiation resulted in statistically significant increases of MST in comparison with the control irradiated mice. Combined administration of IB-MECA and meloxicam was found to be the only treatment statistically enhancing the parameter of CPS and to lead to the most expressive increase in MST of the experimental mice. The findings add new knowledge on the action of an adenosine A3 receptor agonist and a COX-2 inhibitor in an irradiated mammalian organism and suggest the potential of both the investigated drugs in the treatment of the acute radiation damage.

• MeSH
• Adenosine analogs & derivatives   pharmacology   MeSH
• Adenosine A3 Receptor Agonists pharmacology   MeSH
• Time Factors MeSH
• Whole-Body Irradiation adverse effects   MeSH
• Cyclooxygenase 2 metabolism   MeSH
• Cyclooxygenase 2 Inhibitors pharmacology   MeSH
• Drug Interactions MeSH
• Meloxicam MeSH
• Survival Rate MeSH
• Mice MeSH
• Radiation-Protective Agents pharmacology   MeSH
• Receptor, Adenosine A3 metabolism   MeSH
• Thiazines pharmacology   MeSH
• Thiazoles pharmacology   MeSH
• Gamma Rays adverse effects   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adenosine MeSH
• Adenosine A3 Receptor Agonists MeSH
• Cyclooxygenase 2 MeSH
• Cyclooxygenase 2 Inhibitors MeSH
• Meloxicam MeSH
• N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine MeSH Browser
• Radiation-Protective Agents MeSH
• Receptor, Adenosine A3 MeSH
• Thiazines MeSH
• Thiazoles MeSH

This study continues our earlier findings on the hematopoiesis-modulating effects of adenosine A1 and A3 receptor agonists that were performed on committed hematopoietic progenitor and precursor cell populations. In the earlier experiments, N (6)-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, was found to inhibit proliferation in the above-mentioned hematopoietic cell systems, whereas N (6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), an adenosine A3 receptor agonist, was found to stimulate it. The topic of this study was to evaluate the possibility that the above-mentioned adenosine receptor agonists modulate the behavior of early hematopoietic progenitor cells and hematopoietic stem cells. Flow cytometric analysis of hematopoietic stem cells in mice was employed, as well as a functional test of hematopoietic stem and progenitor cells (HSPCs). These techniques enabled us to study the effect of the agonists on both short-term repopulating ability and long-term repopulating ability, representing multipotent progenitors and hematopoietic stem cells, respectively. In a series of studies, we did not find any significant effect of adenosine agonists on HSPCs in terms of their numbers, proliferation, or functional activity. Thus, it can be concluded that CPA and IB-MECA do not significantly influence the primitive hematopoietic stem and progenitor cell pool and that the hematopoiesis-modulating action of these adenosine receptor agonists is restricted to more mature compartments of hematopoietic progenitor and precursor cells.

• MeSH
• Purinergic P1 Receptor Agonists pharmacology   MeSH
• Hematopoietic Stem Cells drug effects   physiology   MeSH
• Hematopoiesis drug effects   physiology   MeSH
• Multipotent Stem Cells drug effects   physiology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Flow Cytometry MeSH
• Receptor, Adenosine A1 metabolism   MeSH
• Receptor, Adenosine A3 metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Purinergic P1 Receptor Agonists MeSH
• Receptor, Adenosine A1 MeSH
• Receptor, Adenosine A3 MeSH

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.

• MeSH
• Hematopoiesis drug effects   MeSH
• Humans MeSH
• Receptors, Purinergic P1 drug effects   MeSH
• Signal Transduction MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Receptors, Purinergic P1 MeSH