ArticleMolecular pain2011
PAP and NT5E inhibit nociceptive neurotransmission by rapidly hydrolyzing nucleotides to adenosine.
Article in Molecular pain, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Immune Cell-Specific Regulatory Gene Prioritization in Low Back Pain Using Single-Cell eQTL-Informed Mendelian Randomization and Colocalization.Journal of pain research · 2026Article
- The cumulative analgesic effect of repeated electroacupuncture is modulated by Adora3 in the SCDH of mice with neuropathic pain.Animal models and experimental medicine · 2025Article
- Dual-Channel Electrochemical Measurements Reveal Rapid Adenosine is Localized in Brain Slices.ACS chemical neuroscience · 2022Article
- Mechanisms of ATP release in pain: role of pannexin and connexin channels.Purinergic signalling · 2021Review
- How Are Adenosine and Adenosine ABiomedicines · 2021Review
- Targeting Adenosine Receptors: A Potential Pharmacological Avenue for Acute and Chronic Pain.International journal of molecular sciences · 2020Review
- Purinergic Signaling in Endometriosis-Associated Pain.International journal of molecular sciences · 2020Review
- CD73 or CD39 Deletion Reveals Different Mechanisms of Formation for Spontaneous and Mechanically Stimulated Adenosine and Sex Specific Compensations in ATP Degradation.ACS chemical neuroscience · 2020Article
- Electrochemistry at the Synapse.Annual review of analytical chemistry (Palo Alto, Calif.) · 2019Review
- Comparison of spontaneous and mechanically-stimulated adenosine release in mice.Neurochemistry international · 2019Article
- Article
- Regional Variations of Spontaneous, Transient Adenosine Release in Brain Slices.ACS chemical neuroscience · 2018Article
- Fast-Scan Cyclic Voltammetry: Chemical Sensing in the Brain and Beyond.Analytical chemistry · 2018Review
- Article
- Caffeine inhibits hypothalamic ANature communications · 2017Article
- CD73 Controls Extracellular Adenosine Generation in the Trigeminal Nociceptive Nerves.Journal of dental research · 2017Article
- Article
- Neuronal NTPDase3 Mediates Extracellular ATP Degradation in Trigeminal Nociceptive Pathway.PloS one · 2016Article
- EXPRESS: NGF-trkA signaling modulates the analgesic effects of prostatic acid phosphatase in resiniferatoxin-induced neuropathy.Molecular pain · 2016Article
- Real time adenosine fluctuations detected with fast-scan cyclic voltammetry in the rat striatum and motor cortex.Journal of neuroscience methods · 2015Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundProstatic acid phosphatase (PAP) and ecto-5'-nucleotidase (NT5E, CD73) produce extracellular adenosine from the nucleotide AMP in spinal nociceptive (pain-sensing) circuits; however, it is currently unknown if these are the main ectonucleotidases that generate adenosine or how rapidly they generate adenosine.
resultsWe found that AMP hydrolysis, when measured histochemically, was nearly abolished in dorsal root ganglia (DRG) neurons and lamina II of spinal cord from Pap/Nt5e double knockout (dKO) mice. Likewise, the antinociceptive effects of AMP, when combined with nucleoside transport inhibitors (dipyridamole or 5-iodotubericidin), were reduced by 80-100% in dKO mice. In addition, we used fast scan cyclic voltammetry (FSCV) to measure adenosine production at subsecond resolution within lamina II. Adenosine was maximally produced within seconds from AMP in wild-type (WT) mice but production was reduced >50% in dKO mice, indicating PAP and NT5E rapidly generate adenosine in lamina II. Unexpectedly, we also detected spontaneous low frequency adenosine transients in lamina II with FSCV. Adenosine transients were of short duration (<2 s) and were reduced (>60%) in frequency in Pap-/-, Nt5e-/- and dKO mice, suggesting these ectonucleotidases rapidly hydrolyze endogenously released nucleotides to adenosine. Field potential recordings in lamina II and behavioral studies indicate that adenosine made by these enzymes acts through the adenosine A1 receptor to inhibit excitatory neurotransmission and nociception.
conclusionsCollectively, our experiments indicate that PAP and NT5E are the main ectonucleotidases that generate adenosine in nociceptive circuits and indicate these enzymes transform pulsatile or sustained nucleotide release into an inhibitory adenosinergic signal.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.