A new neuromodulatory pathway with a glial contribution mediated via A<sub>2a</sub> adenosine receptors

Nishizaki, Tomoyuki; Nagai, Kazuo; Nomura, Tamotsu; Tada, Hitoshi; Kanno, Takeshi; Tozaki, Hidetoshi; Li, X.X.; Kondoh, Takeshi; Kodama, Noriko; Takahashi, Eri; Sakai, Naoto; Tanaka, Kohichi; Saito, Naoaki

doi:10.1002/glia.10100

Cited by 123 publications

(81 citation statements)

References 65 publications

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“…As expected, adenosine causes a 2 -3-fold increase in glutamate release from cultured hippocampal astrocytes from normal rats and mice (7). A similar increase is obtained with cultured astrocytes from GLT-1 knock-out mice and the glutamate release is not inhibited by the GLT-1 inhibitor dehydrokainic acid or by deleting Na + from extracellular solution (7). These demonstrate that the glutamate release is not due to reverse transport by transporters including GLT-1.…”

Section: Glutamate Release From Astrocytes Via a 2a Adenosine Receptorssupporting

confidence: 79%

“…Astrocytes, alternatively, release neurotransmitters in response to an increase in intracellular Ca 2+ concentrations, which in turn stimulates neurons (2 -6). A low concentration (10 nM) of adenosine facilitates hippocampal neurotransmission, where adenosine does not affect synaptically released glutamate and GABA or postsynaptic glutamatergic and GABAergic conductances (7). Adenosine, on the other hand, inhibits functions of the astrocytic glutamate transporter GLT-1 and stimulated glutamate release via A 2 adenosine receptors involving protein kinase A (PKA) activation (7).…”

Section: Astrocytementioning

confidence: 99%

“…A low concentration (10 nM) of adenosine facilitates hippocampal neurotransmission, where adenosine does not affect synaptically released glutamate and GABA or postsynaptic glutamatergic and GABAergic conductances (7). Adenosine, on the other hand, inhibits functions of the astrocytic glutamate transporter GLT-1 and stimulated glutamate release via A 2 adenosine receptors involving protein kinase A (PKA) activation (7). Those actions could enhance synaptic glutamate concentrations, responsible for the facilitatory action of adenosine on hippocampal neurotransmission.…”

Section: Astrocytementioning

confidence: 99%

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ATP- and Adenosine-Mediated Signaling in the Central Nervous System: Adenosine Stimulates Glutamate Release From Astrocytes via A2a Adenosine Receptors

Nishizaki¹

2004

J Pharmacol Sci

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Abstract. Adenosine enhanced intracellular Ca2+ concentrations in astrocytes via A 2a adenosine receptors involving protein kinase A (PKA) activation. The Ca 2+ rise is inhibited by brefeldin A, an inhibitor of vesicular transport; but not by neomycin and U73122, phospholipase C inhibitors; xestospongin, an IP 3 -receptor inhibitor; ryanodine, a ryanodine-receptor inhibitor; TMB-8, an endoplasmic reticulum calcium-release blocker; octanol, a gap-junction inhibitor; or cadmium, a non-selective, calcium-channel blocker. Adenosine stimulates astrocytic glutamate release via an A 2a adenosine receptors / PKA pathway, and the release is inhibited by the vesicular transport inhibitors brefeldin A and bafilomycin A1. A 2a adenosine receptors and the ensuing PKA events, thus, are endowed with vesicular Ca 2+ release from an unknown intracellular calcium store and vesicular glutamate release from astrocytes.

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Section: Glutamate Release From Astrocytes Via a 2a Adenosine Receptorssupporting

confidence: 79%

Section: Astrocytementioning

confidence: 99%

Section: Astrocytementioning

confidence: 99%

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ATP- and Adenosine-Mediated Signaling in the Central Nervous System: Adenosine Stimulates Glutamate Release From Astrocytes via A2a Adenosine Receptors

Nishizaki¹

2004

J Pharmacol Sci

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“…Extracellular ATP directly targets astroglial and neuronal P2X receptors [60] stimulating ATP and glutamate release from astrocytes and modulating the function of postsynaptic receptors [61][62][63][64]. In addition, extracellular adenosine has been shown to induce release of glutamate and NO [65,66] from glial cells. NO, in its turn, enhances vesicular release by stimulating cGMP synthesis at the presynaptic site and upregulates trafficking of AMPA receptors at the postsynaptic site [67].…”

Section: Discussionmentioning

confidence: 99%

Modulation of ATP-induced LTP by cannabinoid receptors in rat hippocampus

Ievglevskyi

Palygin

Kondratskaya

et al. 2012

Purinergic Signalling

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Cannabinoids exert powerful action on various forms of synaptic plasticity. These retrograde messengers modulate GABA and glutamate release from presynaptic terminals by acting on presynaptic CB1 receptors. In particular, they inhibit long-term potentiation (LTP) elicited by electrical stimulation of excitatory pathways in rat hippocampus. Recently, LTP of the field excitatory postsynaptic potential (fEPSP) induced by exogenous ATP has been thoroughly explored. The present study demonstrates that cannabinoids inhibit ATP-induced LTP in hippocampal slices of rat. Administration of 10 μM of ATP led to strong inhibition of fEPSPs in CA1/CA3 hippocampal synapses. Within 40 min after ATP removal from bath solution, robust LTP was observed (fEPSP amplitude comprised 130.1± 3.8% of control, n010). This LTP never appeared when ATP was applied in addition to cannabinoid receptor agonist WIN55,212-2 (100 nM). Selective CB1 receptor antagonist, AM251 (500 nM), completely abolished this effect of WIN55,212-2. Our data indicate that like canonical LTP elicited by electrical stimulation, ATP-induced LTP is under control of CB1 receptors.

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“…Apart from these predominant synaptic effects, it has also been reported that A 2A R can impact on neuronal metabolism [92] but the functional relevance of this finding remains to be explored. Finally, A 2A R are also located in astrocytes and microglia cells [68,93], where they control the uptake of glutamate [94] and the expression of cytokines [68,93].…”

Section: B Adenosine a 2a Receptor Neuromodulation Systemmentioning

confidence: 99%

Role of The Purinergic Neuromodulation System in Epilepsy

Tomé¹,

Silva²,

Cunha³

2010

TONEURJ

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Adenosine has long been considered an endogenous anti-epileptic compound. This concept was based on the widespread distribution of adenosine A 1 receptors (A 1 R), which are mostly located in excitatory synapses; here, A 1 R inhibit glutamate release, decrease glutamatergic responsiveness and hyperpolarise neurons. However, the combined observation that synaptic A 1 R undergo desensitisation in chronic noxious situations whereas the activation of A 1 R still prevents seizure activity suggests that the A 1 R anti-epileptic action may involve non-synaptic mechanisms. Two alternative mechanisms can be considered to explain the ability of A 1 R to control seizure activity and resulting neurodegeneration: 1) the possible role of A 1 R-mediated control of metabolism; 2) the A 1 R-mediated preconditioning involving a coordinated control of neuron-glia communication. However, purinergic modulation of seizure activity is likely to involve other systems apart from A 1 R. Thus, the blockade of adenosine A 2A receptors (A 2A R), which density increases in animal models of epilepsy, can attenuate seizure activity and prevent seizure-induced neurodegeneration. Furthermore, ATP, which is the main source of the endogenous adenosine activating A 2A R, also act as a general danger signal and may also directly control seizure activity through P 2 receptors (P 2 R). Therefore, the purinergic control of epilepsy may actually involve different parallel signalling arms, some beneficial and others deleterious, probably acting at different sites (in epileptic foci and in their neighbourhood) and at different times. It is likely that combined targeting of different purinergic receptors may be the most efficacious way to control seizure activity, its spreading and the resulting neurodegeneration.

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A new neuromodulatory pathway with a glial contribution mediated via A_2a adenosine receptors

Cited by 123 publications

References 65 publications

ATP- and Adenosine-Mediated Signaling in the Central Nervous System: Adenosine Stimulates Glutamate Release From Astrocytes via A2a Adenosine Receptors

ATP- and Adenosine-Mediated Signaling in the Central Nervous System: Adenosine Stimulates Glutamate Release From Astrocytes via A2a Adenosine Receptors

Modulation of ATP-induced LTP by cannabinoid receptors in rat hippocampus

Role of The Purinergic Neuromodulation System in Epilepsy

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A new neuromodulatory pathway with a glial contribution mediated via A2a adenosine receptors

Cited by 123 publications

References 65 publications

ATP- and Adenosine-Mediated Signaling in the Central Nervous System: Adenosine Stimulates Glutamate Release From Astrocytes via A2a Adenosine Receptors

ATP- and Adenosine-Mediated Signaling in the Central Nervous System: Adenosine Stimulates Glutamate Release From Astrocytes via A2a Adenosine Receptors

Modulation of ATP-induced LTP by cannabinoid receptors in rat hippocampus

Role of The Purinergic Neuromodulation System in Epilepsy

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A new neuromodulatory pathway with a glial contribution mediated via A_2a adenosine receptors