Purinergic P2 receptors trigger adenosine release leading to adenosine A2A receptor activation and facilitation of long-term potentiation in rat hippocampal slices

Almeida, Teresa; Rodrigues, Ricardo J.; Mendonça, Alexandre de; Ribeiro, Joaquim A.; Cunha, Rodrigo A.

doi:10.1016/s0306-4522(03)00523-2

Cited by 51 publications

(28 citation statements)

References 61 publications

(73 reference statements)

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“…The A 2A receptor agonist, CGS 21680, facilitated LTP at Schaffer fibers/CA1 pyramid synapses in hippocampal slices [22,23]. When tested at these same synapses, the highly selective A 2A receptor antagonist, SCH 58261 (50 nM), attenuated LTP in vitro [21] and in vivo [24], an effect which was more prominent in aged animals [21].…”

Section: Effects Of Adenosine a 1 Receptor Antagonists And Adenosine mentioning

confidence: 96%

Caffeine, Adenosine Receptors, and Synaptic Plasticity

Costenla

Cunha

Mendonça

2010

JAD

109

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Abstract. Few studies to date have looked at the effects of caffeine on synaptic plasticity, and those that did used very high concentrations of caffeine, whereas the brain concentrations attained by regular coffee consumption in humans should be in the low micromolar range, where caffeine exerts pharmacological actions mainly by antagonizing adenosine receptors. Accordingly, rats drinking caffeine (1 g/L) for 3 weeks, displayed a concentration of caffeine of circa 22 µM in the hippocampus. It is known that selective adenosine A1 receptor antagonists facilitate, whereas selective adenosine A2A receptor antagonists attenuate, long term potentiation (LTP) in the hippocampus. Although caffeine is a non-selective antagonist of adenosine receptors, it attenuates frequency-induced LTP in hippocampal slices in a manner similar to selective adenosine A2A receptor antagonists. These effects of low micromolar concentration of caffeine (30 µM) are maintained in aged animals, which is important when a possible beneficial effect for caffeine in age-related cognitive decline is proposed. Future studies will still be required to confirm and detail the involvement of A1 and A2A receptors in the effects of caffeine on hippocampal synaptic plasticity, using both pharmacological and genetic approaches.

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Section: Effects Of Adenosine a 1 Receptor Antagonists And Adenosine mentioning

confidence: 96%

Caffeine, Adenosine Receptors, and Synaptic Plasticity

Costenla

Cunha

Mendonça

2010

JAD

109

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“…Because P2X receptors contribute to synaptic transmission, mainly at low frequencies of stimulation, they may act as a dynamic low-frequency filter, preventing weak stimuli from inducing long-lasting changes in synaptic efficacy. It has also been claimed that ATP analogs can facilitate LTP through P2 receptor activation that triggers adenosine release, leading to activation of P1 (A 2A ) receptors (Almeida et al, 2003). Large rises in [Ca 2ϩ ] i in CA1 neurons induce LTP, but small rises induce long-term depression (Yamazaki et al, 2002).…”

Section: A Neuroprotectionmentioning

confidence: 99%

Pathophysiology and Therapeutic Potential of Purinergic Signaling

2006

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“…This facilitation is restricted only to tetanised synapses where extracellular ATP is generated in sufficient amounts to activate A 2A receptors (Almeida et al, 2003). This might only occurs upon high-frequency stimulation, characteristic of long-term potentiation.…”

Section: Adenosine As a Synaptic Modulator-a 2a Receptorsmentioning

confidence: 99%

Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity

Cunha

2008

Neurochemistry International

147

129

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Adenosine is a prototypical neuromodulator, which mainly controls excitatory transmission through the activation of widespread inhibitory A 1 receptors and synaptically located A 2A receptors. It was long thought that the predominant A 1 receptor-meditated modulation by endogenous adenosine was a homeostatic process intrinsic to the synapse. New studies indicate that endogenous extracellular adenosine is originated as a consequence of the release of gliotransmitters, namely ATP, which sets a global inhibitory tonus in brain circuits rather than in a single synapse. Thus, this neuron-glia long-range communication can be viewed as a form of non-synaptic transmission (a concept introduced by Professor Sylvester Vizi), designed to reduce noise in a circuit. This neuron-glia-induced adenosine release is also responsible for exacerbating salient information through A 1 receptor-mediated heterosynaptic depression, whereby the activation of a particular synapse recruits a neuron-glia network to generate extracellular adenosine that inhibits neighbouring non-tetanised synapses. In parallel, the local activation of facilitatory A 2A receptors by adenosine, formed from ATP released only at high frequencies from neuronal vesicles, down-regulates A 1 receptors and facilitates plasticity selectively in the tetanised synapse. Thus, upon high-frequency firing of a given pathway, the combined exacerbation of global A 1 receptormediated inhibition in the circuit (heterosynaptic depression) with the local synaptic activation of A 2A receptors in the activated synapse, cooperate to maximise salience between the activated and non-tetanised synapses. #

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Purinergic P2 receptors trigger adenosine release leading to adenosine A2A receptor activation and facilitation of long-term potentiation in rat hippocampal slices

Cited by 51 publications

References 61 publications

Caffeine, Adenosine Receptors, and Synaptic Plasticity

Caffeine, Adenosine Receptors, and Synaptic Plasticity

Pathophysiology and Therapeutic Potential of Purinergic Signaling

Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity

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