2-(4-(2-carboxyethyl)phenethylamino)-5--n-ethylcarboxamidoadenosine and preproenkephalin

In the striatum, adenosine A2A and dopamine D2 receptors exert reciprocal antagonistic interactions that modulate the function of GABAergic enkephalinergic neurons. We have previously shown that stimulation of adenosine A1 receptors allows the stimulation of A2A receptors to overcome a tonic inhibitory effect of D2 receptors and induce striatal expression of c-fos. In the present work, by studying co-localization of c-Fos immunoreactivity and preproenkephalin and preprodynorphin transcripts, we show that co-administration of the A1 receptor agonist CPA and the A2A receptor agonist CGS 21680 increases the striatal expression of c-fos in GABAergic enkephalinergic but not in GABAergic dynorphinergic neurons. Co-administration of CPA and CGS 21680 also induced a significant increase in the striatal expression of preproenkephalin. The results underscore the role of adenosine in the activation of gene expression in the GABAergic enkephalinergic neuron.

Topics: Adenosine; Animals; Corpus Striatum; Drug Combinations; Enkephalins; Gene Expression; Immunohistochemistry; In Situ Hybridization; Male; Neurons; Phenethylamines; Protein Precursors; Proto-Oncogene Proteins c-fos; Purinergic P1 Receptor Agonists; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P1

The effect of adrenalectomy on the expression of adenosine receptors and their mRNA in rat brain was examined using quantitative autoradiography and in situ hybridization. 1,3-[3H]Dipropyl-8-cyclopentylxanthine ([3H]DPCPX), a selective adenosine A1 receptor antagonist, and [3H]CGS 21680, a selective adenosine A(2A) receptor agonist, were used as radioligands. One week after adrenalectomy, the expression of mRNA for adenosine A1 receptors was significantly decreased, as was the number of binding sites for [H]DPCPX. These effects were significantly counteracted by replacement treatment with dexamethasone (1.5 mg/kg i.p., twice daily). Addition of GTP caused a similar increase of [3H]DPCPX binding in sham-operated rats, adrenalectomized rats and rats adrenalectomized and treated with dexamethasone. Moreover, no differences in displacement of [3H]DPCPX by the adenosine receptor agonist N6-(R-phenylisopropyl)adenosine were found among these groups. Adrenalectomy did not significantly affect the number of [3H]CGS 21680 binding sites in striatum or the mRNA encoding adenosine A(2A) receptors. No changes in the affinity of [3H]CGS 21680 for adenosine A(2A) receptors or in the potency of the adenosine receptor agonist 2-chloroadenosine to displace [3H]CGS 21680 were found. Dexamethasone treatment decreased cAMP formation induced by the nonselective adenosine agonist 5'-N-ethylcarboxamidoadenosine in Jurkat cells, which express adenosine A(2B) receptors, but did not alter it in PC-12 cells, which express mostly A(2A) receptors. The results suggest that endogenous corticosteroids positively regulate the expression of adenosine A1 receptors, at least partly at the transcriptional level. In contrast, corticosteroids do not regulate the expression of adenosine A(2A) receptors.

Topics: Adenosine; Adenosine-5'-(N-ethylcarboxamide); Adrenalectomy; Analysis of Variance; Animals; Autoradiography; Brain; Cyclic AMP; Dexamethasone; Enkephalins; Gene Expression; Glucocorticoids; Humans; In Situ Hybridization; Jurkat Cells; Male; Organ Specificity; PC12 Cells; Phenethylamines; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2A; Receptors, Purinergic P1; RNA, Messenger; Transcription, Genetic; Tritium; Xanthines