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Neuronal P2X7Receptors Are Targeted to Presynaptic Terminals in the Central and Peripheral Nervous Systems
Open accessAbstract
The ionotropic ATP receptor subunits P2X(1-6) receptors play important roles in synaptic transmission, yet the P2X(7) receptor has been reported as absent from neurons in the normal adult brain. Here we use RT-PCR to demonstrate that transcripts for the P2X(7) receptor are present in extracts from the medulla oblongata, spinal cord, and nodose ganglion. Using in situ hybridization mRNA encoding, the P2X(7) receptor was detected in numerous neurons throughout the medulla oblongata and spinal cord. Localizing the P2X(7) receptor protein with immunohistochemistry and electron microscopy revealed that it is targeted to presynaptic terminals in the CNS. Anterograde labeling of vagal afferent terminals before immunohistochemistry confirmed the presence of the receptor in excitatory terminals. Pharmacological activation of the receptor in spinal cord slices by addition of 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP; 30 microm) resulted in glutamate mediated excitation of recorded neurons, blocked by P2X(7) receptor antagonists oxidized ATP (100 microm) and Brilliant Blue G (2 microm). At the neuromuscular junction (NMJ) immunohistochemistry revealed that the P2X(7) receptor was present in motor nerve terminals. Furthermore, motor nerve terminals loaded with the vital dye FM1-43 in isolated NMJ preparations destained after application of BzATP (30 microm). This BzATP evoked destaining is blocked by oxidized ATP (100 microm) and Brilliant Blue G (1 microm). This indicates that activation of the P2X(7) receptor promotes release of vesicular contents from presynaptic terminals. Such a widespread distribution and functional role suggests that the receptor may be involved in the fundamental regulation of synaptic transmission at the presynaptic site.
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“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 [50]
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Metadata
- Authors
- Deuchars, S. A., Atkinson, L., Brooke, R. E., Musa, H., Milligan, C. J., Batten, T. F. C., Buckley, N. J., Parson, S. H., & Deuchars, J.
- Affiliations
- University of Leeds (GB)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-09-15
- Volume
- 21
- Issue
- 18
- Pages
- 7143-7152
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762981
- OpenAlex
- W1620679902
- Cited by
- 287
- References
- 53
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4 · 2023: 11 · 2022: 4 · 2021: 8 · 2020: 8 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 9 · 2015: 10 · 2014: 10 · 2013: 13 · 2012: 11
- FWCI
- 9.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- 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 (medical) › Pain Mechanisms and Treatments
- Keywords
- P2X7 receptor, presynaptic terminals, synaptic transmission, medulla oblongata, spinal cord, nodose ganglion, neuromuscular junction, motor nerve terminals, BzATP, oxidized ATP, Brilliant Blue G, glutamate release, vesicle exocytosis
- MeSH terms
- Animals, Central Nervous System, Immunohistochemistry, Male, Medulla Oblongata, Mice, Inbred C57BL, Synaptic Transmission, Neuromuscular Junction, Neurons, Nodose Ganglion, RNA, Messenger, Spinal Cord, Rats, Wistar, In Situ Hybridization, Presynaptic Terminals, Peripheral Nervous System, Receptors, Purinergic P2, Neurotransmitter Agents, Patch-Clamp Techniques, Muscle, Skeletal, Glutamic Acid, Reverse Transcriptase Polymerase Chain Reaction, Mice, Rats, Receptors, Purinergic P2X7
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