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

Changes in brain A(1) and A(2A) receptors and in the corresponding mRNA were studied using quantitative receptor autoradiography and in situ hybridisation. [H-3]-DPCPX was used as an antagonist ligand at A(1) receptors and [H-3]-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 mu M 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.