Pj. Gebickehaerter et al., BOTH ADENOSINE-A1-RECEPTORS AND ADENOSINE-A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION, Neurochemistry international, 29(1), 1996, pp. 37-42
The neuromodulator adenosine is one of the major endogenous inhibitors
of overactive excitatory neurotransmission. Adenosine receptors have
been identified on neuronal but also on glial surfaces, indicating a r
ole of glial cells in mediation of adenosine effects. Microglia, the i
mmunocompetent cells of the brain, typically respond with proliferatio
n, migration and production of inflammatory substances to viral or bac
terial stimuli or to cell damage and degeneration. Since adenosine is
released in large amounts in conditions of, for example, hypoxic or is
chemic stress, it might be involved in the activation process of micro
glia. Proliferation of microglia was determined by incorporation of [H
-3]thymidine into microglial DNA after stimulation with adenosine A1-
and A2-receptor agonists. N-6-Cyclopentyl adenosine (CPA) and CGS-2168
0, a specific adenosine A2-receptor agonist had no effect on microglia
l proliferation. However, combinations of CPA and CGS-21680 as well as
the mixed agonist, N-6-ethyl-carboxamido adenosine (NECA) increased i
ncorporation of radiolabel above controls. The effect of NECA was inhi
bited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-diprop
ylxanthine (DPCPX). From these results, it is concluded that prolifera
tion of microglia can be increased only by simultaneous stimulation of
both adenosine A1- and A2-receptors. Targeted interference with the a
ctivation of A1-adenosine receptors by specific drugs appears to be su
fficient to reduce microglial activation. The findings may have implic
ations for the treatment of neurodegenerative diseases in which microg
lial activation is supposed to play a causative role. Copyright(C) 199
6 Elsevier Science Ltd.