Carbamazepine-induced upregulation of adenosine A(1)-receptors in astrocyte cultures affects coupling to the phosphoinositol signaling pathway

The anticonvulsant and antibipolar drug carbamazepine (CBZ) is known to act as a specific antagonist at adenosine A(1)-receptors. After a 3-week appli cation of CBZ, A(1)-receptors are upregulated in the rat brain. We have inv estigated the consequences of this upregulation for the A(1)-receptor-media ted signal transduction in primary astrocyte cultures from different region s of the rat brain. CBZ treatment for 10 days had no effect on adenosine A( 1)-receptor mRNA expression in cultures with high basal A(1)-receptor mRNA levels, but increased A(1)-receptor mRNA in cultures exhibiting low basal A (1)-receptor mRNA levels. This upregulation of A(1)-receptor mRNA was accom panied by an upregulation or induction of A(1)-receptor-mediated potentiati on of PLC activity, a property that was not found in these cultures before CBZ treatment. Thus, CBZ treatment for 10 days induces a new quality of ade nosine A(1)-receptor-mediated signal transduction in cells that express low basal AI-receptor numbers. [Neuropsychopharmacology 20:271-278, 1999] (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Sci ence Inc.