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Adenosine A 3 receptors in the rat hippocampus: Lack of interaction with A 1 receptors
Author(s) -
Lopes Luísa V.,
Rebola Nelson,
Costenla Ana Rita,
Halldner Linda,
Jacobson Marlene A.,
Oliveira Catarina R.,
Richardson Peter J.,
Fredholm Bertil B.,
Ribeiro Joaquim A.,
Cunha Rodrigo A.
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10188
Subject(s) - receptor , hippocampal formation , neurotransmission , agonist , adenosine a1 receptor , long term depression , 5 ht1 receptor , chemistry , glutamate receptor , adenosine , adenosine receptor , neuroscience , medicine , endocrinology , biology , metabotropic receptor , biochemistry , ampa receptor
Abstract 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.