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Journal of Neuroscience, Vol 15, 6103-6109, Copyright © 1995 by Society for Neuroscience
Growth factor upregulation of a phosphoinositide-coupled metabotropic glutamate receptor in cortical astrocytes
S Miller, C Romano and CW Cotman
Department of Psychobiology, University of California, Irvine 92717- 4550, USA.
CNS function depends on a capacity for plasticity during development,
following injury, and in response to changing environmental conditions.
Functional alterations in signal transduction pathways and in
neurotransmitter receptor expression are possible mechanisms for the
expression of such plasticity. In the present report, we demonstrate that
exposure of astrocytes to specific growth factors alters both the
functional activity and the protein levels of a specific glutamate
receptor. Exposure of astrocytes to basic fibroblast growth factor,
epidermal growth factor, or transforming growth factor-alpha produced
marked increases in the ability of metabotropic glutamate receptor (mGluR)
agonists to stimulate phosphoinositide hydrolysis. Using Western
immunoblotting, we demonstrate that an increase in the levels of one of the
phosphoinositide-coupled mGluR subtypes, mGluR5, accompanies the increased
ability of mGluR agonists to stimulate phosphoinositide hydrolysis. In
contrast, another phosphoinositide- coupled subtype of this receptor
family, mGluR1 alpha, was not present at detectable levels in these
cultures. The enhanced stimulation of phosphoinositide hydrolysis showed
little sensitivity to pertussis toxin, and appeared to be selective to
mGluR agonists, as there was not a similar increase in the ability of
norepinephrine or carbachol to stimulate phosphoinositide hydrolysis. These
findings demonstrate that expression of mGluRs in astrocytes is plastic,
and indicate a novel pathway through which specific growth factors may
selectively modulate neurotransmitter action.
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