Adenosine A(2A) 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 inhibito ry A(1) receptors but also via facilitatory A(2A) receptors. We now investi gated the transducing system operated by hippocampal A(2A) receptors. The s elective A(2A) receptor agonist, CGS 21680 (10 nM), facilitated synaptic tr ansmission by 14%, an effect not modified by the phosphodiesterase IV inhib itor, rolipram (30 mu M), or by the adenylate cyclase activator, forskolin (3 mu M), or by the protein kinase A inhibitor, HA-1004 (10 mu M), but near ly abolished by the protein kinase C inhibitors, chelerythrine (6 mu M) or bisindolylmaleimide I (1 mu M). Inhibition of protein kinase C also prevent ed the A(2A) receptor-induced attenuation of A(1) receptormediated inhibiti on of hippocampal synaptic transmission. These results indicate that adenos ine A(2A) receptor facilitation of hippocampal synaptic transmission involv es protein kinase C rather than protein kinase A activation. (C) 2000 Elsev ier Science Ireland Ltd. All rights reserved.