The cellular localization of adenosine receptors in rat neostriatum

Abstract

Using quantitative autoradiography of ligand binding sites combined with lesions of specific neuronal pathways, the cellular locations of A1 and A2 adenosine receptors, as well as a third binding site for the adenosine receptor ligand, [3H]N-ethylcarboxamidoadenosine, and a nucleoside transporter were investigated in rat neostriatum. Intrastriatal kainic acid administration resulted in the loss of 50% of A1 adenosine receptors and virtually abolished ligand binding to A2 receptors. A small reduction in [3H]cyclohexyladenosine binding to striatal A1 receptors was found after lesioning the corticostriatal input. A2 receptor sites were unaffected by this treatment. Destruction of dopaminergic neurons using 6-hydroxydopamine or the raphestriatal serotoninergic input using 5,7-dihydroxytryptamine affected neither A1 nor A2 binding sites. These results indicate the localization of both A1 and A2 adenosine receptors on neurons intrinsic to the neostriatum and probably postsynaptic to the dopaminergic input. In addition, a binding site for [3H]N-ethylcarboxamidoadenosine which is not affected by the adenosine receptor agonist, R-phenylisopropyladenosine, was also partly abolished after kainic acid injection. In contrast, no significant change in the binding of the nucleoside transporter ligand, [3H]nitrobenzylthioinosine, was observed after any lesions, indicating the widespread association of this site with various cell types.