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Cited by 24Adenosine and Purinergic SignalingNeuroscience and Neuropharmacology ResearchPain Mechanisms and Treatments

Under stressful conditions activation of the ionotropic P2X7 receptor differentially regulates GABA and glutamate release from nerve terminals of the rat cerebral cortex

Barros-Barbosa, Aurora R., Oliveira, Ângela, Lobo, M. Graça, Cordeiro, J. Miguel, Correia-de-Sá, Paulo·2018·Neurochemistry International
DOI 10.1016/j.neuint.2017.11.005
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Abstract

γ-Aminobutyric acid (GABA) and glutamate (Glu) are the main inhibitory and excitatory neurotransmitters in the central nervous system (CNS), respectively. Fine tuning regulation of extracellular levels of these amino acids is essential for normal brain activity. Recently, we showed that neocortical nerve terminals from patients with epilepsy express higher amounts of the non-desensitizing ionotropic P2X7 receptor. Once activated by ATP released from neuronal cells, the P2X7 receptor unbalances GABAergic vs. glutamatergic neurotransmission by differentially interfering with GABA and Glu uptake. Here, we investigated if activation of the P2X7 receptor also affects [3 H]GABA and [14 C]Glu release measured synchronously from isolated nerve terminals (synaptosomes) of the rat cerebral cortex. Data show that activation of the P2X7 receptor consistently increases [14 C]Glu over [3 H]GABA release from cortical nerve terminals, but the GABA/Glu ratio depends on extracellular Ca 2+ concentrations. While the P2X7-induced [3 H]GABA release is operated by a Ca 2+-dependent pathway when external Ca 2+ is available, this mechanism shifts towards the reversal of the GAT1 transporter in low Ca 2+ conditions. A different scenario is verified regarding [14 C]Glu outflow triggered by the P2X7 receptor, since the amino acid seems to be consistently released through the recruitment of connexin-containing hemichannels upon P2X7 activation, both in the absence and in the presence of external Ca 2+. Data from this study add valuable information suggesting that ATP, via P2X7 activation, not only interferes with the high-affinity uptake of GABA and Glu but actually favors the release of these amino acids through distinct molecular mechanisms amenable to differential therapeutic control.

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  • Studies in pure neuronal cell cultures and synaptosomes confirm that stimulation of P2X7R expressed in nerve terminals favors glutamate and GABA release.

    “The effects mediated by P2X7R in glial cells and adenosine can be avoided in studies in pure neuronal cell cultures [106] and synaptosomes [107,108,109], which confirms that stimulation of P2X7R expressed in nerve terminals favors glutamate and GABA release.”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [109]

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Authors
Barros-Barbosa, A. R., Oliveira, Â., Lobo, M. G., Cordeiro, J. M., & Correia-de-Sá, P.
Affiliations
Universidade do Porto (PT)
ORCID
Venue
Neurochemistry International
Publisher
Elsevier BV
Published
2018-01
Volume
112
Pages
81-95
ISSN
0197-0186 (ISSN-L)
DOI
10.1016/j.neuint.2017.11.005
OpenAlex
W2769975599
Cited by
24
References
55
Citations by year
2026: 3 · 2025: 1 · 2024: 6 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 1
FWCI
1.47
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurochemistry International (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Porto/Santander Totta
  • Liga Portuguesa Contra a Epilepsia (LPCE)
  • Tecnifar and Fundação para a Ciência e a Tecnologia (PEst-OE/SAU/UI0215/2014, UID/BIM/4308/2016)
  • FCT Portugal CIÊNCIA 2008 Programme (CONT_DOUT/117/ICBAS-UP/215/10824/2/2008)
  • FCT (SFRH/BD/79259/2011)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
P2X7 receptor, GABA release, glutamate release, synaptosomes, ATP, extracellular calcium, glutamate uptake, connexin hemichannels, epilepsy, neurotransmitter release
MeSH terms
Adenosine Triphosphate, Animals, Cerebral Cortex, Dose-Response Relationship, Drug, gamma-Aminobutyric Acid, Nerve Endings, Stress, Psychological, Synaptosomes, Presynaptic Terminals, Glutamic Acid, Rats, Receptors, Purinergic P2X7

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