The cellular localization of adenosine receptors in rat neostriatum

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Using quantitative autoradiography of ligand binding sites combined with lesions of specific neuronal pathways, the cellular locations of A 1 and A 2 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 A 1 adenosine receptors and virtually abolished ligand binding to A 2 receptors. A small reduction in [ 3H]cyclohexyladenosine binding to striatal A 1 receptors was found after lesioning the corticostriatal input. A 2 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 A 1, nor A 2 binding sites. These results indicate the localization of both A 1 and A 2 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.