Chronic theophylline treatment increases adenosine A1, but not A2, receptor binding in the rat brain: an autoradiographic study.

Chronic exposure to adenosine receptor antagonists results in an upregulation of brain adenosine A1 receptors as measured by traditional radioligand binding techniques. In the present study, quantitative receptor autoradiography was used to characterize alterations in rat brain adenosine A1 and A2 receptors following the repeated administration of high doses of theophylline. Daily administration of theophylline (75 or 100 mg/kg) markedly increased (125-150% of control) 1 nM [3H]cyclohexyladenosine binding to adenosine A1 receptors in specific cellular layers of the hippocampus, thalamus, and cerebellum with other brain regions showing more moderate increases in binding. By contrast, this chronic theophylline treatment did not produce any significant alterations in the binding of 4 nM [3H]CGS 21680 to adenosine A2 receptors, which were exclusively localized in the striatal region. This apparent differential sensitivity of adenosine receptor subtypes to chronic antagonist treatment suggests a possible intrinsic difference in the regulation of these receptor subtypes which may also be specific to particular brain regions. These results are discussed in relationship to other recent observations, indicating that the pattern of agonist binding to adenosine receptors may be regulated by a differential extent of coupling between adenosine receptors and G-binding proteins in different brain regions.