Interactions between adenosine and metabotropic glutamate receptors in the rat hippocampal slice

1. We have examined excitatory postsynaptic potentials and paired-pulse interactions in rat hippocampal slices to obtain more information about the site and mechanism of interactions between metabotropic glutamate receptors and adenosine receptors. 2. The results show that the suppression of adenosine sensitivity is explained by a selectively reduced responsiveness to A(1) receptor stimulation, and does not involve any facilitation of A(2A) adenosine receptors, since it can be obtained in the absence of endogenous adenosine and is not prevented by the A(2A) receptor blocker ZM241385. 3. The glutamate receptors involved are of the group I class since the suppression of adenosine sensitivity is produced by ACPD and the group I selective compound DHPG. Furthermore, the effects of DHPG could be prevented by LY367385, a selective antagonist at the mGlu(1a) subtype of group I receptors. The selective antagonist at mGlu(5) receptors, SIB1893, did not prevent the suppression of adenosine sensitivity by DHPG. Blockade of the DHPG/adenosine interaction was also obtained by superfusion with the protein kinasae C inhibitor chelerythrine. 4. Since the suppression of adenosine responses by metabotropic receptor agonists was seen in the paired-pulse paradigm, we conclude that the observed interactions occur at the level of the presynaptic terminals. 5. The interaction with adenosine receptors is not specific, but applies also to a suppression of responses mediated by the GABA(B) receptor agonist baclofen. 6. We conclude that activation of the mGlu1a subtype of receptor can suppress responses mediated via adenosine A1 receptors, probably by activating protein kinase C. Since the changes induced by metabotropic glutamate receptor agonists last for at least 60 min, the data also imply that these interactions could play an important role in changes of synaptic function long after even transient increases of glutamate release in the CNS.