ArticleJournal of molecular neuroscience : MN
Neutral endopeptidase knockout induces hyperalgesia in a model of visceral pain, an effect related to bradykinin and nitric oxide.
Article in Journal of molecular neuroscience : MN. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- A comprehensive review of the literature on CD10: its function, clinical application, and prospects.Frontiers in pharmacology · 2024Review
- Neprilysin expression and functions in development, ageing and disease.Mechanisms of ageing and development · 2020Review
- Nitric oxide in the gastrointestinal tract: opportunities for drug development.British journal of pharmacology · 2019Review
- Neprilysin Inhibitors and Bradykinin.Frontiers in medicine · 2018Review
- Long-term neprilysin inhibition - implications for ARNIs.Nature reviews. Cardiology · 2017Review
- Nociceptor-Enriched Genes Required for Normal Thermal Nociception.Cell reports · 2016Article
- The Alzheimer's amyloid-degrading peptidase, neprilysin: can we control it?International journal of Alzheimer's disease · 2012Article
- Article
- Kyotorphin transport and metabolism in rat and mouse neonatal astrocytes.Brain research · 2010Article
- The Analgesic Activity of Bestatin as a Potent APN Inhibitor.Frontiers in neuroscience · 2010Article
- Improved learning and memory in aged mice deficient in amyloid beta-degrading neutral endopeptidase.PloS one · 2009Article
- The roles of streptozotocin neurotoxicity and neutral endopeptidase in murine experimental diabetic neuropathy.Experimental diabetes research · 2009Article
- Aminopeptidase N in arterial hypertension.Heart failure reviews · 2008Review
- Use of preproenkephalin knockout mice and selective inhibitors of enkephalinases to investigate the role of enkephalins in various behaviours.Psychopharmacology · 2008Article
- Reduced fertility in male mice deficient in the zinc metallopeptidase NL1.Molecular and cellular biology · 2004Article
- Vasopeptidase inhibitor ilepatril (AVE7688) prevents obesity- and diabetes-induced neuropathy in C57Bl/6J mice.NeuropharmacologyArticle
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutral endopeptidase (EC3.4.24.11, NEP, enkephalinase) is a zinc-metalloendopeptidase, cleaving a variety of substrates like enkephalins, substance P, and bradykinin. In the brain, NEP is a key enzyme in the degradation of enkephalins. Pharmacological inhibition of NEP-activity causes analgesia resulting from enhanced extracellular enkephalin concentrations. Recently, transgenic mice lacking the enzyme NEP have been developed (Lu, 1995). The present study was designed to investigate the nociceptive behavior of these NEP-knockout mice. Interestingly, NEP-deficient mice did not respond with decreased pain perception, but exhibited hyperalgesia in the hot-plate jump, warm-water tail-withdrawal, and mostnotablyin theacetic-acid writhing test. Inhibition of aminopeptidase N by bestatin reduced writhing in both strains, whereas NEP-inhibition by thiorphan reduced writhing selectively in wild-type mice. Naloxone increased writhing in wild-type but not in knockouts, whereas the bradykinin B2-receptor antagonist HOE140 reduced writhing selectively in NEP-knockouts. Similarly, the nitric oxide synthase inhibitor L-NAME reduced writhing in NEP-knockouts. These results indicate that genetic elimination of NEP, in contrast to pharmacological inhibition, leads to bradykinin-induced hyperalgesia instead of enkephalin-mediated analgesia. Nitric oxide (NO) is suggested to be involved in this process.
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