Regulation of Adenosine Receptors in Rat Brain following Chronic Carbamazepine Treatment<SUP>&#12548;</SUP>

Regulation of Adenosine Receptors in Rat Brain following Chronic Carbamazepine Treatment<SUP>&#12548;</SUP>

<P> Carbamazepine (CBZ), an anticonvulsant, has beeen reported to displace ligands at adenosine receptors. Several studies have demonstrated that as far as A<SUB>2</SUB> adenosine receptors is concerned, CBZ acts as an antagonist. However, the situation with regard to A<SUB>1</SUB> receptors is less straightforward. In this study, we describe the effects of one-week CBZ treatment (25 mg/kg/day) on cerebrocortical A<SUB>1</SUB> adenosine receptors. A<SUB>1</SUB> adenosine receptor bindings as determined by using [<SUP>3</SUP>H]DPCPX was not significantly altered in membranes prepared from CBZ-treated rats. However, there was a significant decrease in the A<SUB>1 </SUB>adenosine receptor-mediated stimulation of [<SUP>35</SUP>S]GTP<SUB>γ</SUB>S binding to cerebrocortical membranes prepared from CBZ-treated rats (20.0% decrease in basal activity; 17.8% decrease in maximal activity). The basal and 10<SUP>-4</SUP> M forskolin-stimulated adenylyl cyclase activities were relatively unaffected by CBZ treatment, but 10 mM NaF-stimulated adenylyl cyclase activity was significantly reduced in CBZ-treated rats. It appears that one-week CBZ treatment caused an uncoupling of adenosine receptors from G proteins without alteration of A<SUB>1</SUB> adenosine receptor molecules, suggesting that CBZ acts as an agonist at A<SUB>1 </SUB>adenosine receptors in rat brain.