Adenosine A3 receptors in the rat hippocampus:: Lack of interaction with A1 receptors

Adenosine acts as a neuromodulator in the hippocampus essentially through activation of inhibitory A(1) receptors. Using single-cell PCR analysis, we found that CA1 pyramidal cells coexpress A(1) receptor mRNA together with that of another adenosine receptor, the A(3) receptor. As occurs for the A(1) receptor, Western blot analysis indicated that the A(3) receptor is also located in hippocampal nerve terminals. However, activation of A(3) receptors with its purportedly selective agonist CI-IBMECA (0.1-10 muM) failed to affect hippocampal synaptic transmission or to modify the evoked release of glutamate or GABA. Also, blockade of A(3) receptors with MRS 1191 (5 muM) failed to affect either hypoxia- or ischemia-induced depression of hippocampal synaptic transmission. Activation of A(3) receptors also failed to control A(1) receptor function, as CI-IBMECA (100 nM) did not modify the ability of CPA to displace [H-3]DPCPX binding to hippocampal membranes or the A(1) receptor-mediated inhibition of hippocampal synaptic transmission. However, ligand binding studies revealed that CI-IBMECA displaced the binding of an A(1) receptor agonist ([H-3]R-PIA, K-i = 47 nM) or antagonist ([H-3]DPCPX, K-i = 130 nM), which suggests that A(3) receptor ligands also act on native A(1) receptors. We believe that A(3) receptors are expressed in hippocampal neurons and are located in hippocampal nerve terminals, though their function remains elusive. (C) 2003 Wiley-Liss, Inc.