Article date: March 2004
By: Luísa V Lopes, Linda Halldner, Nelson Rebola, Björn Johansson, Catherine Ledent, Jian Fan Chen, Bertil B Fredholm, Rodrigo A Cunha in Volume 141, Issue 6, pages 1006-1014
2‐p‐(2‐carboxyethylphenethylamino‐5′‐ethylcarboxamidoadenosine) (CGS 21680) is considered the reference compound to study adenosine A2A receptors. However, CGS 21680 binding in the cerebral cortex, where adenosine A1 receptors are predominant, displays a mixed A2A/A1 receptor pharmacology. We now use adenosine A1 and A2A receptor knockout mice to investigate the characteristics of cortical [3H]CGS 21680 binding.
[3H]CGS 21680 binding to the cerebral cortex was strongly reduced in adenosine A1 receptor knockout mice, but only slightly reduced in A2A receptor knockout mice compared with the corresponding wild‐type littermates.
Another selective A2A receptor ligand, [3H]‐5‐amino‐7‐(2‐phenylethyl)‐2‐(2‐furyl)‐pyrazolo[4,3‐e]‐1,2,4‐triazolo[1,5‐c]pyrimidine ([3H]SCH 58261), displayed a saturable binding to mouse cortical membranes, albeit with a binding density 20 times lower than that of striatal membranes, and this [3H]SCH58261 binding was abolished in both striatal and cortical membranes of A2A receptor knockout mice and unchanged in A1 receptor knockout mice.
The presence of A2A receptors in cortical neurons was further confirmed by Western blot in mouse cortical nerve terminal membranes.
It is concluded that, although A2A receptors are present in the cerebral cortex, the purportedly selective A2A receptor agonist [3H]CGS 21680 binds in the cerebral cortex to an entity that requires the presence of adenosine A1 receptors. Thus, CGS 21680 should be used with care in all preparations where adenosine A1 receptors out‐number A2A receptors.
2‐p‐(2‐carboxyethylphenethylamino‐5′‐ethylcarboxamidoadenosine) (CGS 21680) is considered the reference compound to study adenosine A2A receptors. However, CGS 21680 binding in the cerebral cortex, where adenosine A1 receptors are predominant, displays a mixed A2A/A1 receptor pharmacology. We now use adenosine A1 and A2A receptor knockout mice to investigate the characteristics of cortical [3H]CGS 21680 binding.
[3H]CGS 21680 binding to the cerebral cortex was strongly reduced in adenosine A1 receptor knockout mice, but only slightly reduced in A2A receptor knockout mice compared with the corresponding wild‐type littermates.
Another selective A2A receptor ligand, [3H]‐5‐amino‐7‐(2‐phenylethyl)‐2‐(2‐furyl)‐pyrazolo[4,3‐e]‐1,2,4‐triazolo[1,5‐c]pyrimidine ([3H]SCH 58261), displayed a saturable binding to mouse cortical membranes, albeit with a binding density 20 times lower than that of striatal membranes, and this [3H]SCH58261 binding was abolished in both striatal and cortical membranes of A2A receptor knockout mice and unchanged in A1 receptor knockout mice.
The presence of A2A receptors in cortical neurons was further confirmed by Western blot in mouse cortical nerve terminal membranes.
It is concluded that, although A2A receptors are present in the cerebral cortex, the purportedly selective A2A receptor agonist [3H]CGS 21680 binds in the cerebral cortex to an entity that requires the presence of adenosine A1 receptors. Thus, CGS 21680 should be used with care in all preparations where adenosine A1 receptors out‐number A2A receptors.
British Journal of Pharmacology (2004) 141, 1006–1014. doi:10.1038/sj.bjp.0705692
DOI: 10.1038/sj.bjp.0705692
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