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

Changes in brain A1 and A2A 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 A1 receptors and [3H]-CGS 21680 as an agonist ligand at A2A receptors. Treatment of rats with the relatively A1 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 A1 receptor ligand, but not in that of the A2A receptor ligand. The effect on A1 receptors was also seen in the presence of 100 microM GTP that decreases agonist binding to insignificant levels. There was no change in either A1 or A2A 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 A1 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.