Involvement of P2X7 receptors in the regulation of neurotransmitter release in the rat hippocampus

Sperlágh, Beáta; Köfalvi, Attila; Deuchars, Jim; Atkinson, Lucy; J. Milligan, Carol; Buckley, Noel J.; Vizi, E. Sylvester

doi:10.1046/j.1471-4159.2002.00920.x

Cited by 264Adenosine and Purinergic SignalingNeuroscience and Neuropharmacology ResearchPain Mechanisms and Treatments

Involvement of P2X7 receptors in the regulation of neurotransmitter release in the rat hippocampus

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Sperlágh, Beáta, Köfalvi, Attila, Deuchars, Jim, Atkinson, Lucy, J. Milligan, Carol, Buckley, Noel J., Vizi, E. Sylvester·2002·Journal of Neurochemistry

DOI 10.1046/j.1471-4159.2002.00920.x

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Abstract

Although originally cloned from rat brain, the P2X7 receptor has only recently been localized in neurones, and functional responses mediated by these neuronal P2X7 receptors (P2X7 R) are largely unknown. Here we studied the effect of P2X7 R activation on the release of neurotransmitters from superfused rat hippocampal slices. ATP (1-30 mm) and other ATP analogues elicited concentration-dependent [3 H]GABA outflow, with the following rank order of potency: benzoylbenzoylATP (BzATP) > ATP > ADP. PPADS, the non-selective P2-receptor antagonist (3-30 microm), Brilliant blue G (1-100 nm) the P2X7 -selective antagonist and Zn2+ (0.1-30 microm) inhibited, whereas lack of Mg2+ potentiated the response by ATP. In situ hybridization revealed that P2X7 R mRNA is expressed in the neurones of the cell body layers in the hippocampus. P2X7 R immunoreactivity was found in excitatory synaptic terminals in CA1 and CA3 region targeting the dendrites of pyramidal cells and parvalbumin labelled structures. ATP (3-30 microm) and BzATP (0.6-6 microm) elicited concentration-dependent [14 C]glutamate efflux, and blockade of the kainate receptor-mediated transmission by CNQX (10-100 microm) and gadolinium (100 microm), decreased ATP evoked [3 H]GABA efflux. The Na+ channel blocker TTX (1 microm), low temperature (12 degrees C), and the GABA uptake blocker nipecotic acid (1 mm) prevented ATP-induced [3 H]GABA efflux. Brilliant blue G and PPADS also reduced electrical field stimulation-induced [3 H]GABA efflux. In conclusion, P2X7 Rs are localized to the excitatory terminals in the hippocampus, and their activation regulates the release of glutamate and GABA from themselves and from their target cells.

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P2X7R is detected in glial and neuronal cells.
“Despite being detected in glial and neuronal cells [49,50,51,52,53,54], the activity of the P2X7R was not always investigated and used antibodies lack specificity [49,55,56,57].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [51]
P2X7R antagonists (BBG or PPADS) reduced GABA release elicited by both ATP and electric stimulation.
“P2X7R antagonists (BBG or PPADS) reduced GABA release elicited by both ATP and electric stimulation [51].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [51]

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“2003), followed by increased glutamate and subsequent c-aminobutyric acid (GABA) release (Alloisio et al. 2008; Papp et al. 2004; Patti et al. 2006; Sperlagh et al. 2002).”
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Authors: Sperlágh, B., Köfalvi, A., Deuchars, J., Atkinson, L., J. Milligan, C., Buckley, N. J., & Vizi, E. S.
Affiliations: HUN-REN Institute of Experimental Medicine (HU)
University of Leeds (GB)
Corresponding author: Sperlágh, Beáta
ORCID: Sperlágh, Beáta
Köfalvi, Attila
Deuchars, Jim
Buckley, Noel J.
Vizi, E. Sylvester
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2002-06-06
Volume: 81
Issue: 6
Pages: 1196-1211
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1046/j.1471-4159.2002.00920.x
OpenAlex: W1574063361
Cited by: 264
References: 83
Citations by year: 2026: 3 · 2025: 8 · 2024: 10 · 2023: 15 · 2022: 8 · 2021: 14 · 2020: 10 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 8 · 2015: 12 · 2014: 10 · 2013: 14 · 2012: 15
FWCI: 8.85
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Egészségügyi Tudományos Tanács
Volkswagen Foundation
Hungarian Scientific Research Fund
National Institutes of Health
Medical Research Council
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, ATP, neurotransmitter release, hippocampus, GABA release, glutamate release, Brilliant Blue G, PPADS, kainate receptors, parvalbumin interneurons, pyramidal neurons, zinc, magnesium, ATP analogs
MeSH terms: Adenosine Triphosphate, Animals, gamma-Aminobutyric Acid, Hippocampus, Immunohistochemistry, Male, Nerve Endings, Neurons, Subcellular Fractions, Receptors, Purinergic P2, Neurotransmitter Agents, Excitatory Amino Acids, Rats, Receptors, Purinergic P2X7, In Vitro Techniques

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Involvement of P2X7 receptors in the regulation of neurotransmitter release in the rat hippocampus

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