ArticlePloS one2013
Proteolysis controls endogenous substance P levels.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Exosomes from mesenchymal stem/stromal cells and their therapeutic role in osteoarthritic pain.Journal of experimental orthopaedics · 2026Article
- The effect of substance P and its common in vivo-formed metabolites on MRGPRX2 and human mast cell activation.Pharmacology research & perspectives · 2022Article
- Measuring behavioral and physiological responses to pain mitigation for ovariectomy in Bos taurus yearling beef heifers.Journal of animal science · 2020Article
- Neuropeptides: important regulators of joint homeostasis.Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA · 2019Review
- A Chitosan-Based Liposome Formulation Enhances the In Vitro Wound Healing Efficacy of Substance P Neuropeptide.Pharmaceutics · 2017Article
- The angiotensin converting enzyme inhibitor, captopril, prevents the hyperactivity and impulsivity of neurokinin-1 receptor gene 'knockout' mice: sex differences and implications for the treatment of attention deficit hyperactivity disorder.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2015Article
- Increasing substance P levels in serum and synovial tissues from patients with developmental dysplasia of the hip (DDH).BMC musculoskeletal disorders · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Substance P (SP) is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP from neurons. Proteolysis has long been suspected to regulate extracellular SP concentrations but data in support of this hypothesis is scarce. Here, we provide evidence that proteolysis controls SP levels in the spinal cord. Using peptidomics to detect and quantify endogenous SP fragments, we identify the primary SP cleavage site as the C-terminal side of the ninth residue of SP. If blocking this pathway increases SP levels, then proteolysis controls SP concentration. We performed a targeted chemical screen using spinal cord lysates as a proxy for the endogenous metabolic environment and identified GM6001 (galardin, ilomastat) as a potent inhibitor of the SP(1-9)-producing activity present in the tissue. Administration of GM6001 to mice results in a greater-than-three-fold increase in the spinal cord levels of SP, which validates the hypothesis that proteolysis controls physiological SP levels.
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What OpenQuestion holds
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.