ArticleThe Journal of pharmacology and experimental therapeutics2011
4-oxo-2-nonenal (4-ONE): evidence of transient receptor potential ankyrin 1-dependent and -independent nociceptive and vasoactive responses in vivo.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Lipid Peroxidation Products 4-ONE and 4-HNE Modulate Voltage-Gated Sodium Channels in Neuronal Cell Lines and DRG Action Potentials.Antioxidants (Basel, Switzerland) · 2026Article
- Mechanisms and Recent Advances of Small-Molecule Therapeutics in Rosacea Treatment.Clinical, cosmetic and investigational dermatology · 2025Review
- Treatment of rosacea with upadacitinib and abrocitinib: case report and review of evidence for Janus kinase inhibition in rosacea.Frontiers in immunology · 2024Review
- Expression of Trpa1 and Trpv1 Genes in the Hypothalamus and Blood Pressure in Normotensive and Hypertensive Rats. Effect of Losartan and Captopril.Bulletin of experimental biology and medicine · 2023Article
- Transient Receptor Potential Channel Ankyrin 1: A Unique Regulator of Vascular Function.Cells · 2021Review
- Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models.International journal of molecular sciences · 2020Article
- Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Cardiovascular Diseases.Frontiers in physiology · 2020Review
- Regulation of vascular tone by transient receptor potential ankyrin 1 channels.Current topics in membranes · 2020Review
- Article
- The TRPA1 Channel in the Cardiovascular System: Promising Features and Challenges.Frontiers in pharmacology · 2019Review
- Skin neurogenic inflammation.Seminars in immunopathology · 2018Review
- Relevance of TRPA1 and TRPM8 channels as vascular sensors of cold in the cutaneous microvasculature.Pflugers Archiv : European journal of physiology · 2018Article
- Capsaicin-Sensitive Sensory Nerves Mediate the Cellular and Microvascular Effects of H2S via TRPA1 Receptor Activation and Neuropeptide Release.Journal of molecular neuroscience : MN · 2016Article
- TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO.British journal of pharmacology · 2016Article
- Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner.Arthritis research & therapy · 2016Article
- Synergistic Effect of Ferulic Acid and Z-Ligustilide, Major Components of A. sinensis, on Regulating Cold-Sensing Protein TRPM8 and TPRA1 In Vitro.Evidence-based complementary and alternative medicine : eCAM · 2016Article
- Polysulfide evokes acute pain through the activation of nociceptive TRPA1 in mouse sensory neurons.Molecular pain · 2015Article
- Article
- TRPA1 is essential for the vascular response to environmental cold exposure.Nature communications · 2014Article
- Cinnamaldehyde inhibits L-type calcium channels in mouse ventricular cardiomyocytes and vascular smooth muscle cells.Pflugers Archiv : European journal of physiology · 2014Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
This study explores the in vivo effects of the proposed transient receptor potential ankyrin 1 (TRPA1) agonist 4-oxo-2-nonenal (4-ONE). Pharmacological inhibitors and genetically modified mice were used to investigate the ability of 4-ONE to act via TRPA1 receptors and possible mechanisms involving transient receptor potential vanilloid 1 (TRPV1). We hypothesized that 4-ONE activates sensory nerves, via TRPA1 or possibly TRPV1, and thus triggers mechanical hyperalgesia, edema formation, and vasodilatation in mice. An automated dynamic plantar aesthesiometer was used to determine hind paw withdrawal thresholds, and a laser Doppler flowmeter was used to measure skin blood flow. Edema formation was determined by measuring paw weights and thickness. 4-ONE (10 nmol) triggers unilateral mechanical hyperalgesia, edema formation, and vasodilatation in mice and is shown here to exhibit TRPA1-dependent and -independent effects. Neurogenic vasodilatation and mechanical hyperalgesia at 0.5 h postinjection were significantly greater in TRPA1 wild-type (WT) mice compared with TRPA1 knockout (KO) mice. Edema formation throughout the time course as well as mechanical hyperalgesia from 1 to 4 h postinjection were similar in WT and TRPA1 KO mice. Studies involving TRPV1 KO mice revealed no evidence of TRPV1 involvement or interactions between TRPA1 and TRPV1 in mediating the in vivo effects of 4-ONE. Previously, 4-ONE was shown to be a potent TRPA1 agonist in vitro. We demonstrate its ability to mediate vasodilatation and certain nociceptive effects in vivo. These data indicate the potential of TRPA1 as an oxidant sensor for vasodilator responses in vivo. However, 4-ONE also triggers TRPA1-independent effects that relate to edema formation and pain.
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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.