ArticleThe Journal of clinical investigation2014
Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 102 citations in OpenAlex.
- Immunopathogenesis of itch: an integrative framework for chronic pruritus.JID innovations : skin science from molecules to population health · 2026Review
- Broadening the View: Substance P and Its Metabolism in Pruritus-Related Diseases.The Journal of dermatology · 2026Review
- From neuroimmune circuits to targeted therapy of chronic pruritus.Pharmacological reviews · 2026Review
- Transient Receptor Potential (TRP) Channels as Fundamental Regulators of Fibrosis and Pruritus-A New Therapeutic Target for Pathological Scar Management.International journal of molecular sciences · 2026Review
- A Natural Composite Extract Restores Skin Barrier Function by Modulating Inflammatory, Hydration, and Redox Pathways.Journal of cosmetic dermatology · 2025Article
- Keratinocyte-TRPV1 sensory neuron interactions in a genetically controllable mouse model of chronic neuropathic itch.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Therapeutic effect of bosentan on 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model.Archives of dermatological research · 2025Article
- An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma.Clinical and experimental medicine · 2023Review
- Pruritogenic Mediators and New Antipruritic Drugs in Atopic Dermatitis.Journal of clinical medicine · 2023Review
- Pruritogens in pemphigoid diseases: Possible therapeutic targets for a burdensome symptom.The Journal of dermatology · 2023Review
- Molecular mechanisms of pruritus in prurigo nodularis.Frontiers in immunology · 2023Review
- Transient Receptor Potential Channels and Itch.International journal of molecular sciences · 2022Review
- Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment.International journal of molecular sciences · 2022Review
- Critical Players and Therapeutic Targets in Chronic Itch.International journal of molecular sciences · 2022Review
- Role of ERK Pathway in the Pathogenesis of Atopic Dermatitis and Its Potential as a Therapeutic Target.International journal of molecular sciences · 2022Article
- Pruritus: A Sensory Symptom Generated in Cutaneous Immuno-Neuronal Crosstalk.Frontiers in pharmacology · 2022Review
- Microinjection of pruritogens in NGF-sensitized human skin.Scientific reports · 2021Article
- Role of Mast Cells in the Pathogenesis of Pruritus in Mastocytosis.Acta dermato-venereologica · 2021Article
- Review
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 6 countries.
Funding
Abstract
In humans, pruritus (itch) is a common but poorly understood symptom in numerous skin and systemic diseases. Endothelin 1 (ET-1) evokes histamine-independent pruritus in mammals through activation of its cognate G protein-coupled receptor endothelin A receptor (ETAR). Here, we have identified neural endothelin-converting enzyme 1 (ECE-1) as a key regulator of ET-1-induced pruritus and neural signaling of itch. We show here that ETAR, ET-1, and ECE-1 are expressed and colocalize in murine dorsal root ganglia (DRG) neurons and human skin nerves. In murine DRG neurons, ET-1 induced internalization of ETAR within ECE-1-containing endosomes. ECE-1 inhibition slowed ETAR recycling yet prolonged ET-1-induced activation of ERK1/2, but not p38. In a murine itch model, ET-1-induced scratching behavior was substantially augmented by pharmacological ECE-1 inhibition and abrogated by treatment with an ERK1/2 inhibitor. Using iontophoresis, we demonstrated that ET-1 is a potent, partially histamine-independent pruritogen in humans. Immunohistochemical evaluation of skin from prurigo nodularis patients confirmed an upregulation of the ET-1/ETAR/ECE-1/ERK1/2 axis in patients with chronic itch. Together, our data identify the neural peptidase ECE-1 as a negative regulator of itch on sensory nerves by directly regulating ET-1-induced pruritus in humans and mice. Furthermore, these results implicate the ET-1/ECE-1/ERK1/2 pathway as a therapeutic target to treat pruritus in humans.
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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.