Adaptive changes in adenosine receptors following long-term treatment with the adenosine receptor agonist R-phenylisopropyl adenosine

Abstract

Changes in brain a 1 and A 2A receptors and in the corresponding mRNA were studied using quantitative receptor autoradiography and in situ hybridisation. [ 3H]-DPCPX was used as an antagonist ligand at A 1 receptors and [ 1H]-CGS 21680 as an agonist ligand at A 2A receptors. Treatment of rats with the relatively a 1 receptor selective adenosine analogue R-PIA (0.3 mg/kg) for 7 days in the presence of the peripherally acting antagonist 8-p-sulfophenyltheophylline (8-PST;10 mg/kg) caused a decrease in the binding of the a 1 receptor ligand, but not in that of the A 2A receptor ligand. The effect on a 1 receptors was also seen in the presence of 100 μM GTP that decreases agonist binding to insignificant levels. There was no change in either a 1 or A 2A receptor mRNA. No significant changes were detected following administration of either R-PIA or 8-PST alone. These results thus demonstrate an effect on brain a 1 receptors after systemic administration of R-PIA in the presence of a peripherally acting adenosine antagonist, demonstrating that, under these conditions, the agonist reaches receptors in significant amounts.