Evidence for functionally important adenosine A2a receptors in the rat hippocampus

doi:10.1016/0006-8993(94)91066-9

Brain Research

Volume 649, Issues 1–2, 27 June 1994, Pages 208-216

https://doi.org/10.1016/0006-8993(94)91066-9 Get rights and content

Abstract

Adenosine A_2a receptors are not confined to dopamine-rich areas of the brain, since thermocycling analysis shows that adenosine A_2a receptor mRNA is expressed also in the hippocampus (CA1, CA3 and dentate gyrus) and cerebral cortex. The expression of A_2a mRNA in three main areas of the hippocampus was confirmed by in situ hybridization; A_2a mRNA expression was mainly localized in the pyramidal and granular cells, the same hippocampal regions that showed adenosine A₁ receptor mRNA expression. Receptor autoradiographic studies with [³H]CGS 21680 (30 nM), a selective adenosine A_2a receptor agonist, showed specific binding sites in the hippocampus. The density of [³H]CGS 21680 binding was greatest in the stratum radiatum of the CA1 area, followed by the stratum oriens of the cornu Ammonis, stratum radiatum of the CA3 area and supra-granular layer of the dentate gyrus. This antomical distribution of [³H]CGS 21680 binding was similar to the pattern of [³H]CHA binding in the hippocampus. Electrophysiological studies in the Schaffer fibers / CA1 pyramids showed that upon activation of the A_2a receptors with CGS 21680 (10 nM) the ability of the adenosine A₁ receptor agonist, CPA, to inhibit neuronal activity was significantly attenuated. These results show functionally important co-expression of adenosine A_2a and A₁ receptors in the hippocampus. The results also suggest that adenosine A_2a receptor-mediated neuromodulation is not confined to the basal ganglia, but is more widespread throughout the nervous system.

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Adenosine is the endogenous purine nucleoside that arise from the hydrolysis of ATP and in the CNS it is mainly an inhibitory neurotransmitter. In the hippocampal pyramidal cells and the dentate gyrus (DG) granule cells, there are highly expressed A1 inhibitory receptors and less abundant A2A receptors with facilitatory effect (Cunha et al., 1994; Kim & Johnston, 2015; Madroñal, Delgado-Garcia, & Gruart, 2007; Merighi, Gessi, & Borea, 2018). Both receptor types are coupled to G proteins and contain one central domain that passes the membrane 7 times (Merighi et al., 2018).
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Evidence for functionally important adenosine A2a receptors in the rat hippocampus

Abstract

Int. Rev. Neurobiol.

Neuroscience

Mol. Brain Res.

Mol. Brain Res.

Eur. J. Pharmacol.

Eur. J. Pharmacol. Sect.

Neuroscience

Neuron

Neurosci. Lett.

Neurosci. Lett.

Neurochem. Int.

Brain Res.

Neurosci. Lett.

Neurosci. Lett.

Both A1 and A2a purine receptors regulate striatal acetylcholine release

J. Neurochem.

Inhibitory and excitatory effects of adenosine receptor agonists on evoked transmitter release from phrenic nerve endings of the rat

Br. J. Pharmacol.

Evidence for functionally important adenosine A_2a receptors in the rat hippocampus

Both A₁ and A_2a purine receptors regulate striatal acetylcholine release