Effects of Stable Adenosine
Receptor Agonists on Bone Marrow Hematopoietic Cells as Inferred
from the Cytotoxic Action of 5-Fluorouracil
M. POSPÍŠIL, M. HOFER, A. VACEK, V. ZNOJIL1, I.
PIPALOVÁ1
Institute of Biophysics, Academy of Sciences of the Czech
Republic, and 1Medical Faculty, Masaryk University,
Brno, Czech Republic
Received August 26, 2003
Accepted October 25, 2003
Summary
The aim of the study was to investigate the effects of stable
adenosine receptor agonists on bone marrow hematopoiesis by
utilizing the model of hematopoietic damage induced by
5-fluorouracil (5-FU), a cycle-specific cytotoxic agent. Effects
of a non-selective agonist NECA activating all the known
adenosine receptors (A1, A2A, A2B, A3) and of the selective
agonists for A1 (CPA), A2A (CGS 21680), and A3 (IB-MECA)
adenosine receptors were investigated. Experiments were
performed with B10CBAF1 mice under in vivo conditions. Adenosine
receptor agonists were given in single injections before 5-FU
administration and the effects were determined 4 days later. The
numbers of femoral marrow nucleated cells and hematopoietic
progenitor cells (CFC-GM and BFU-E) were taken as indices of the
effects. The non-selective agonist NECA given at a dose of 200
nmol/kg induced biphasic time-dependent effects, i.e. protection
and sensitization, when given 10 h and 22 h before 5-FU
administration, respectively. The use of isomolar doses of
selective receptor agonists indicated that the protective
effects of NECA were induced by activation of A2A and A2B
receptors, while the sensitizing action of NECA was mediated via
A3 receptors. In addition, it was observed that A1 receptors
induced protection when activated by administration of CPA 22 h
before 5-FU. These findings are discussed with respect to the
action of adenosine receptor agonists on the cell cycle state
and on the cell cycle-independent cellular protective
mechanisms.
Key words
Adenosine receptor agonists • Hematopoiesis • 5-Fluorouracil
|