The "regulators of
g-protein signalling" (RGS) comprise a large family of
proteins that limit by virtue of their
GTPase accelerating protein domain the signal transduction of
G-protein coupled receptors.
RGS proteins have been implicated in various neuropsychiatric diseases such as
schizophrenia,
drug abuse, depression and anxiety and aggressive behaviour. Since conditions associated with a large increase of
adenosine in the brain such as
seizures or
ischemia were reported to modify the expression of some
RGS proteins we hypothesized that
adenosine might regulate RGS expression in neural cells. We measured the expression of RGS-2,-3, and -4 in both transformed glia cells (human U373 MG
astrocytoma cells) and in primary rat astrocyte cultures stimulated with
adenosine agonists. Expression of RGS-2
mRNA as well as RGS2
protein was increased up to 30-fold by
adenosine agonists in astrocytes. The order of potency of agonists and the blockade by the
adenosine A2B-antagonist
MRS1706 indicated that this effect was largely mediated by
adenosine A2B receptors. However, a smaller effect was observed due to activation of
adenosine A2A receptors. In
astrocytoma cells
adenosine agonists elicited an increase in RGS-2 expression solely mediated by A2B receptors. Expression of RGS-3 was inhibited by
adenosine agonists in both
astrocytoma cells and astrocytes. However while this effect was mediated by A2B receptors in
astrocytoma cells it was mediated by A2A receptors in astrocytes as assessed by the order of potency of agonists and selective blockade by the specific antagonists
MRS1706 and
ZM241385 respectively. RGS-4 expression was inhibited in
astrocytoma cells but enhanced in astrocytes by
adenosine agonists.