Adenosine A2A receptor facilitation of synaptic transmission in the CA1 area of the rat hippocampus requires protein kinase C but not protein kinase A activation.

Adenosine is a neuromodulator in the hippocampus acting mainly via inhibitory A(1) receptors but also via facilitatory A(2A) receptors. We now investigated the transducing system operated by hippocampal A(2A) receptors. The selective A(2A) receptor agonist, CGS 21680 (10 nM), facilitated synaptic transmission by 14%, an effect not modified by the phosphodiesterase IV inhibitor, rolipram (30 microM), or by the adenylate cyclase activator, forskolin (3 microM), or by the protein kinase A inhibitor, HA-1004 (10 microM), but nearly abolished by the protein kinase C inhibitors, chelerythrine (6 microM) or bisindolylmaleimide I (1 microM). Inhibition of protein kinase C also prevented the A(2A) receptor-induced attenuation of A(1) receptor-mediated inhibition of hippocampal synaptic transmission. These results indicate that adenosine A(2A) receptor facilitation of hippocampal synaptic transmission involves protein kinase C rather than protein kinase A activation.