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Vol. 280, Issue 2, 1094-1101, 1997

Glucocorticoids Regulate the Expression of Adenosine A1 but not A2A Receptors in Rat Brain

Per Svenningsson1 and Bertil B. Fredholm

Department of Physiology and Pharmacology, Section of Molecular Neuropharmacology, Karolinska Institutet, Stockholm, Sweden

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 A2A 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 [3H]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 A2A receptors. No changes in the affinity of [3H]CGS 21680 for adenosine A2A 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 A2B receptors, but did not alter it in PC-12 cells, which express mostly A2A 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 A2A receptors.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


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