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

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 mM) 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 mM) failed to affect either hypoxia-or ischemiainduced depression of hippocampal synaptic transmission. Activation of A 3 receptors also failed to control A 1 receptor function, as Cl-IBMECA (100 nM

Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats

“…The activation of A3 receptors by adenosine may also desensitize A1 receptors. A3 receptors are present in rat hippocampal nerve terminal membranes (Lopes et al, 2003).…”

The A3 adenosine receptor as multifaceted therapeutic target: pharmacology, medicinal chemistry, and in silico approaches

“…59 Instead, in cortical neurons the A 3 AR activation depresses the signal transmission by inhibiting glutamate release independently from A 1 AR providing neuroprotection. 60,61 Interestingly, some contrasting evidence was reported in astroglia, where nanomolar concentrations of the A 3 AR agonist Cl-IB-MECA provided neuroprotection, while micromolar doses induced apoptosis. 62 It seems that astrocyte destruction is aimed at isolating the damaged areas [63][64][65][66] through the stimulation of caspase 3.…”

“…Finally, compound 57 showed comparable good profile at the hA 3 AR. In the Elzein's series (58)(59)(60)(61)(62), compounds 59, 61, and 62 displayed high binding affinities (K i hA 3 AR$2.0 nM) and selectivities for the hA 3 AR (hA 1 /hA 3 Z900 and hA 2A /hA 3 Z1,200). In this specific series, it was found that at the N 6 -position of the 2-pyrazolyl adenosine analog, the methyl group was optimal for high hA 3 AR binding affinity and selectivity.…”

Caffeine, Adenosine Receptors, and Synaptic Plasticity

“…Regarding adenosine A 3 receptors, their level of expression in the brain is low [26], albeit they are located in hippocampal nerve terminals [27]. Nevertheless, one study showed that an adenosine A 3 receptor agonist, Cl-IBMECA (100 nM), could increase LTP at Schaffer fibers/CA1 pyramid synapses in vitro, an effect prevented by a selective A 3 receptor antagonist, MRS 1191 (10 µM).…”