Effects of the selective adenosine A2 receptor agonist CGS 21680 on in vitro electrophysiology, cAMP formation and dopamine release in rat hippocampus and striatum

Evaluation of adenosine A2 receptor function in the mammalian CNS has been impeded by the lack of highly selective A2 receptor agonists. The present investigations describe the actions of a recently introduced A2 selective adenosine agonist, CGS 21680 (2-[p-(carboxyethyl)phenylethylamino]-5'-N- ethylcarboxamidoadenosine), on various function neural responses known to be affected by adenosine. In hippocampal slices, CGS 21680 appeared to be a weak agonist on pre- and postsynaptic measures of electrophysiological activity (putative A1 receptor mediated events) and was ineffective at stimulating the formation of cAMP (a putative A2(b) mediated response. 5'-N-ethylcarboxamidoadenosine (NECA), which is known to act at both A2(a) and A2(b) receptors, increased hippocampal cAMP levels 4-fold. In striatal slices, CGS 21680 potently stimulated the formation of cAMP with an EC₅₀ of 110 nM but was ineffective at inhibiting electrically stimulated dopamine release. In contrast, adenosine and cyclohexyladenosine both inhibited the stimulus-evoked overflow of dopamine. These results agree with previous receptor binding studies suggesting that CGS 21680 is a relatively selective agonist at the high affinity adenosine A2(a) receptor in striatum, with little intrinsic activity at the low affinity A2(b) site in hippocampus.