Chronic theophylline exposure increases agonist and antagonist binding to A₁ adenosine receptors in rat brain

Chronic treatment of rats with theophylline (75 mg/kg twice-daily for 21 consecutive days) significantly increased the specific binding of [^3HCHA and [³H]DPCPX in cerebral cortical membranes. The absolute increase in the number of binding sites following theophylline treatment was approximately the same for each ligand, although this number represents a larger percentage of the total sites available to [³H]CHA. Saturation analysis of [³H]DPCPX binding indicated that theophylline treatment increased the maximum number of binding sites from 799 ± 13 to 920 ± 22 fmol/mg protein, while the affinity of [³H]DPCPX for A₁ receptors was unaltered.These results suggest that chronic theophylline exposure produces both an increase in the number of A₁ adenosine receptors and an enhancement of coupling of these receptors to G proteins.