ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Tissue-nonspecific alkaline phosphatase acts redundantly with PAP and NT5E to generate adenosine in the dorsal spinal cord.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
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- The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.Biomarker research · 2025Review
- Broad Vitamin BInternational journal of molecular sciences · 2025Article
- Genetic Insights Into Coronary Microvascular Disease.Microcirculation (New York, N.Y. : 1994) · 2025Review
- Adenosine receptors on the immuno-oncology expressway: TIME, perspectives, and translation.Frontiers in immunology · 2025Review
- Ectonucleotidases and purinergic receptors in mouse prostate gland.American journal of clinical and experimental urology · 2025Article
- CD73/adenosine axis exerts cardioprotection against hypobaric hypoxia-induced metabolic shift and myocarditis in a sex-dependent manner.Cell communication and signaling : CCS · 2024Article
- Elusive physiological role of prostatic acid phosphatase (PAP): generation of choline for sperm motility via auto-and paracrine cholinergic signaling.Frontiers in physiology · 2023Review
- The adenosinergic machinery in cancer: In-tandem insights from basic mechanisms to therapy.Frontiers in immunology · 2023Review
- Urinary ATP Levels Are Controlled by Nucleotidases Released from the Urothelium in a Regulated Manner.Metabolites · 2022Article
- Overcoming high level adenosine-mediated immunosuppression by DZD2269, a potent and selective A2aR antagonist.Journal of experimental & clinical cancer research : CR · 2022Article
- Enzyme histochemistry: a useful tool for examining the spatial distribution of brain ectonucleotidases in (patho)physiological conditions.Histology and histopathology · 2022Review
- Altered Topographic Distribution and Enhanced Neuronal Expression of Adenosine-Metabolizing Enzymes in Rat Hippocampus and Cortex from Early to late Adulthood.Neurochemical research · 2022Article
- The Role of Microglial Purinergic Receptors in Pain Signaling.Molecules (Basel, Switzerland) · 2022Review
- Dual-Channel Electrochemical Measurements Reveal Rapid Adenosine is Localized in Brain Slices.ACS chemical neuroscience · 2022Article
- TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.Cardiovascular research · 2022Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Prostatic acid phosphatase (PAP) and ecto-5'-nucleotidase (NT5E) hydrolyze extracellular AMP to adenosine in dorsal root ganglia (DRG) neurons and in the dorsal spinal cord. Previously, we found that adenosine production was reduced, but not eliminated, in Pap⁻/⁻/Nt5e⁻/⁻ double knock-out (dKO) mice, suggesting that a third AMP ectonucleotidase was present in these tissues. Here, we found that tissue-nonspecific alkaline phosphatase (TNAP, encoded by the Alpl gene) is expressed and functional in DRG neurons and spinal neurons. Using a cell-based assay, we found that TNAP rapidly hydrolyzed extracellular AMP and activated adenosine receptors. This activity was eliminated by MLS-0038949, a selective pharmacological inhibitor of TNAP. In addition, MLS-0038949 eliminated AMP hydrolysis in DRG and spinal lamina II of dKO mice. Using fast-scan-cyclic voltammetry, we found that adenosine was rapidly produced from AMP in spinal cord slices from dKO mice, but virtually no adenosine was produced in spinal cord slices from dKO mice treated with MLS-0038949. Last, we found that AMP inhibited excitatory neurotransmission via adenosine A1 receptor activation in spinal cord slices from wild-type, Pap⁻/⁻, Nt5e⁻/⁻, and dKO mice, but failed to inhibit neurotransmission in slices from dKO mice treated with MLS-0038949. These data suggest that triple elimination of TNAP, PAP, and NT5E is required to block AMP hydrolysis to adenosine in DRG neurons and dorsal spinal cord. Moreover, our data reveal that TNAP, PAP, and NT5E are the main AMP ectonucleotidases in primary somatosensory neurons and regulate physiology by metabolizing extracellular purine nucleotides.
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Registered trials
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.