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Regular Manuscript

Homeostatic action of adenosine A3 and A1 receptor agonists on proliferation of hematopoietic precursor cells

Michal Hofer ^1*, Milan Pospíil ¹, Vladimír Znojil ², Jiina Holá ¹, Denisa Streitová ¹, and Antonín Vacek ¹

¹ Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic
² Institute of Pathological Physiology, Medical Faculty, Masaryk University

^* To whom correspondence should be addressed. E-mail: hofer{at}ibp.cz.

	Abstract

Two adenosine receptor agonists, i.e., N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) and N6-cyclopentyladenosine (CPA) activating selectively adenosine A3 and A1 receptors, respectively, were tested for their ability to influence proliferation of granulocytic and erythroid cells in femoral bone marrow of mice when using morphological criteria. Agonists were given ip to mice in repeated isomolar doses of 200 nmol/kg. Three variants of experiments were performed including investigations of the action of the agonists under normal resting state of mice and in phases of cell depletion and subsequent regeneration after treatment with the cytotoxic drug 5-fluorouracil. In case of granulopoiesis, IB-MECA increased moderately but significantly proliferation of cells under normal resting state, strongly increased proliferation of cells in the phase of cell depletion, but did not influence cell proliferation in the phase of regeneration. CPA did not influence cell proliferation under normal resting state and in the phase of cell depletion, but strongly suppressed the oveshooting cell proliferation in the phase of regeneration. As concerns erythroid cells, the only stimulatory effect of IB-MECA on cell proliferation was observed when administering this agonist in the phase of cell depletion. CPA did not modulate erythroid proliferation in any of the functional states investigated, probably due to the lower demand for cell production as compared with granulopoiesis. The results indicate opposite effects of the two adenosine receptor agonists on proliferation of hematopoietic cells and suggest the plasticity and homeostatic role of the adenosine receptor expression.

Key Words: adenosine receptors, hematopoiesis, cell proliferation