[3H]SCH 58261, a Selective Adenosine A2A Receptor Antagonist, Is a Useful Ligand in Autoradiographic Studies

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Abstract
We have characterized the new potent and selective nonxanthine adenosine A2A receptor antagonist SCH 58261 as a new radioligand for receptor autoradiography. In autoradiographic studies using agonist radioligands for A2A receptors ([3H]CGS 21680) or A1 receptors (N6‐[3H]cyclohexyladenosine), it was found that SCH 58261 is close to 800‐fold selective for rat brain A2A versus A1 receptors (Ki values of 1.2 nM versus 0.8 µM). Moreover, receptor autoradiography showed that [3H]SCH 58261, in concentrations below 2 nM, binds only to the dopamine‐rich regions of the rat brain, with a KD value of 1.4 (0.8–1.8) nM. The maximal number of binding sites was 310 fmol/mg of protein in the striatum. Below concentrations of 3 nM, the nonspecific binding was 3H]SCH 58261 with the following estimated Ki values (nM): 2‐hex‐1‐ynyl‐5′‐N‐ethylcarboxamidoadenosine, 3.9 (1.8–8.4); CGS 21680, 130 (42–405); N6‐cyclohexyladenosine, 9,985 (3,169–31,462). The binding of low concentrations of SCH 58261 was not influenced by either GTP (100 µM) or Mg2+ (10 mM). The present results show that in its tritium‐labeled form, SCH 58261 appears to be a good radioligand for autoradiographic studies, because it does not suffer from some of the problems encountered with the currently used agonist radioligand [3H]CGS 21680.

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