Effects of adenosine A 3 receptor agonist on bone marrow granulocytic system in 5-fluorouracil-treated mice

• Published in: European journal of pharmacology Vol. 538; no. 1; pp. 163 - 167
• Main Authors: Hofer, Michal, Pospíšil, Milan, Vacek, Antonín, Holá, Jiřina, Znojil, Vladimír, Weiterová, Lenka, Štreitová, Denisa
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2006
• Subjects: 5-Fluorouracil; Adenosine A 3 receptor; Granulopoiesis; Mouse; Myelosuppression; 5-Fluorouracil; Mouse; Adenosine A 3 receptor; Myelosuppression; Granulopoiesis
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.03.042

The purpose of the experiments reported was to investigate effects of N 6-(3-iodobenzyl)adenosine-5’- N-methyluronamide (IB-MECA), a selective adenosine A 3 receptor agonist, on the granulocytic system in femoral marrow of mice depleted by the cytotoxic drug 5-fluorouracil. In the phase of the highest cell depletion IB-MECA was injected i.p. at single doses of 200 nmol/kg given either once or twice daily in 2- and 4-day regimens starting on day 1 after 5-fluorouracil administration; the effects were evaluated on days 3 and 5, respectively. The general effect of IB-MECA in all these experiments was an enhancement of the counts of morphologically recognizable proliferative granulocytic cells, interpreted as evidence of the differentiation of committed progenitor cells. A more expressive effect was observed after IB-MECA injected twice daily. It was found that the induction of the strong differentiation pressures by IB-MECA given twice daily shortly after 5-fluorouracil treatment can be counterproductive due to the preponderance of differentiaton processes over the proliferation control. In additional experiments, it has been shown that the use of the 2-day administration of IB-MECA given twice daily in the recovery phase, i.e., on days 5 and 6 after 5-fluorouracil administration, does not induce stimulatory effects. Thus, the dosing and timing of IB-MECA treatment determines its effectivity in stimulating granulopoiesis under conditions of myelosuppression.