The selective adenosine A2A receptor antagonist SCH 58261 discriminates between two different binding sites for [3H]-CGS 21680 in the rat brain.

We have used quantitative autoradiography to further examine two previously described binding sites for [3H]-CGS 21680 in cortical regions and in striatum, respectively. The striatal binding sites largely represent classical adenosine A2A receptors whereas the cortical sites show characteristics that differ from those of recognised adenosine receptors. A recently developed non-xanthine A2A receptor antagonist SCH 58261 displaced the binding of [3H]-CGS 21680 from the A2A receptors in striatum with an estimated Ki value of 2.4 nM, but was more than 1000-fold less potent in displacing its binding from cortex. Conversely, the adenosine analogue 2-chloro-NECA was found to be some 10 times more potent in displacing CGS 21680 from the cortical binding sites than from A2A receptors. The results provide additional evidence that CGS 21680 binds not only to classical A2A receptors, but also to sites that differ from defined adenosine receptors. They also suggest that effects of CGS 21680 observed in the presence of SCH 58261 might reveal the functional significance (if any) of these sites.