GROWTH-FACTOR UP-REGULATION OF A PHOSPHOINOSITIDE-COUPLED METABOTROPIC GLUTAMATE-RECEPTOR IN CORTICAL ASTROCYTES

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 neurot ransmitter receptor expression are possible mechanisms for the express ion of such plasticity. In the present report, we demonstrate that exp osure of astrocytes to specific growth factors alters both the functio nal activity and the protein levels of a specific glutamate receptor. Exposure of astrocytes to basic fibroblast growth factor, epidermal gr owth factor, or transforming growth factor-alpha produced marked incre ases in the ability of metabotropic glutamate receptor (mGluR) agonist s to stimulate phosphoinositide hydrolysis, Using Western immunoblotti ng, we demonstrate that an increase in the levels of one of the phosph oinositide-coupled mGluR subtypes, mGluR5, accompanies the increased a bility of mGluR agonists to stimulate phosphoinositide hydrolysis. In contrast, another phosphoinositide-coupled subtype of this receptor fa mily, mGluR1 alpha, was not present at detectable levels in these cult ures. The enhanced stimulation of phosphoinositide hydrolysis showed l ittle 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 fa ctors may selectively modulate neurotransmitter action.