Adenosine receptor-coupled adenylate cyclase in the caudate nucleus of the rat brain.
5'-(N-Ethylcarboxamido)adenosine (NECA) and N6-[(R)-(phenylisopropyl)]adenosine (PIA) were incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen tissue of the rat, in order to examine the effect of kainic acid and a 6-hydroxydopamine-induced lesion on adenosine receptor coupled adenylate cyclase in vitro. There was an enhancement of formation of cyclic AMP induced by NECA, that was mediated by A2 adenosine receptors. Phenylisopropyl adenosine also stimulated adenylate cyclase in the striatum, with a maximum increase at 0.1 mM. At smaller concentrations, PIA inhibited the basal activity, which was previously described to be an effect mediated by A1 adenosine receptors. In caudate-putamen tissue from rats receiving a unilateral lesion, induced with kainic acid, basal and maximally NECA- and PIA-stimulated activity of adenylate cyclase was decreased. The maximum stimulatory effects of both substances were also significantly decreased, whereas no change of the inhibitory effect of PIA was observed. After unilateral lesion induced with 6-OHDA, basal and maximally NECA- and PIA-activated adenylate cyclase was increased; however, no inhibitory effect of PIA was seen. These results suggest that A2 adenosine receptor-coupled adenylate cyclase was located on neurones intrinsic to the neostriatum and probably postsynaptic to the dopaminergic input. The A1 adenosine receptors seem to be associated with the nigrostriatal pathway implying a presynaptic localization on dopaminergic afferents. In addition, since after both kainic acid- and 6-OHDA-induced lesions, respectively, in caudate-putamen tissue of the contralateral side, PIA no longer inhibited the activity of adenylate cyclase, contralateral structures also appeared to be involved in the regulation of A1 adenosine receptors.
Department of Neurology, Medical University of Lübeck, Germany.
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Moser
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Liebetrau
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Cramer
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002421:Caudate Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D016627:Oxidopamine; D000262:Adenylyl Cyclases; D000241:Adenosine; D007608:Kainic Acid