Effects of adenosine A(3) receptor agonist on bone marrow granulocytic system in 5-fluorouracil-treated mice.
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.
Hofer
Michal
M
Laboratory of Experimental Hematology, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic. hofer@ibp.cz
Pospísil
Milan
M
Vacek
Antonín
A
Holá
Jirina
J
Znojil
Vladimír
V
Weiterová
Lenka
L
Streitová
Denisa
D
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D013997:Time Factors
D058909:Adenosine A3 Receptor Agonists; D007166:Immunosuppressive Agents; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000241:Adenosine; D005472:Fluorouracil