Effects of Adenosine A(3) Receptor Agonist on Bone Marrow Granulocytic System in 5-fluorouracil-treated Mice.
From: Laboratory of Experimental Hematology, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic. hofer@ibp.cz
European journal of pharmacology
- Publish Date: May 2006
- ISSN: 0014-2999
- Volume: 538
- Issue: 1-3
- Pages: 163-7
- Medium: Print
- Language: English
- Citation (JAMA): Hofer Michal, Pospísil Milan, Vacek Antonín, et al. Effects of Adenosine A(3) Receptor Agonist on Bone Marrow Granulocytic System in 5-fluorouracil-treated Mice.. Eur. J. Pharmacol. May 2006;538:163-7
Abstract
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.
Mesh Headings (Keywords): Adenosine, Animals, Bone Marrow Cells, Cell Proliferation, Fluorouracil, Granulocytes, Immunosuppressive Agents, Injections, Intraperitoneal, Male, Mice, Receptor, Adenosine A3, Time Factors
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