Adenosine A 3 receptors in the rat hippocampus: Lack of interaction with A 1 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 Cl‐IBMECA (0.1–10 µM) 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 µM) 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 Cl‐IBMECA (100 nM) did not modify the ability of CPA to displace [ 3 H]DPCPX binding to hippocampal membranes or the A 1 receptor‐mediated inhibition of hippocampal synaptic transmission. However, ligand binding studies revealed that Cl‐IBMECA displaced the binding of an A 1 receptor agonist ([ 3 H]R‐PIA, K i =47 nM) or antagonist ([ 3 H]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. Drug Dev. Res. 58:428–438, 2003. © 2003 Wiley‐Liss, Inc.