ArticleBritish journal of pharmacology2014
The tyrosine kinase inhibitor bafetinib inhibits PAR2-induced activation of TRPV4 channels in vitro and pain in vivo.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Targeting druggable kinases in neuropathic pain.npj drug discovery · 2026Review
- Modulation of Nociceptive Ion Channels by Protease-Activated Receptor-2 in Inflammatory Pain: Molecular Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Endosomal MrGPRX1 signaling sensitizes TRPV1 to enhance itch.Frontiers in molecular neuroscience · 2026Article
- Endosomal MrGPRX1 signaling sensitizes TRPV1 to enhance itch.bioRxiv : the preprint server for biology · 2025Article
- The role of protease-activated receptors (PARs) in the functioning of platelets and platelet-derived microparticles (PMPs).Frontiers in molecular biosciences · 2025Review
- Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Roles of mechanosensitive ion channels in immune cells.Heliyon · 2024Review
- Update on protease-activated receptor 2 in inflammatory and autoimmune dermatological diseases.Frontiers in immunology · 2024Review
- The Role of the TRPV4 Channel in Intestinal Physiology and Pathology.Journal of inflammation research · 2024Review
- Protease-Activated Receptor 2 (PAR2) Expressed in Sensory Neurons Contributes to Signs of Pain and Neuropathy in Paclitaxel Treated Mice.The journal of pain · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- TRP Channels: Recent Development in Translational Research and Potential Therapeutic Targets in Migraine.International journal of molecular sciences · 2022Review
- Article
- Serotonin-induced vascular permeability is mediated by transient receptor potential vanilloid 4 in the airways and upper gastrointestinal tract of mice.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Recent Advances in Pain Management: Relevant Protein Kinases and Their Inhibitors.Molecules (Basel, Switzerland) · 2021Review
- PAR2 Deficiency Induces Mitochondrial ROS Generation and Dysfunctions, Leading to the Inhibition of Adipocyte Differentiation.Oxidative medicine and cellular longevity · 2021Article
- Cough as an adverse effect on inhalation pharmaceutical products.British journal of pharmacology · 2020Review
- Novel airway smooth muscle-mast cell interactions and a role for the TRPV4-ATP axis in non-atopic asthma.The European respiratory journal · 2020Article
- Review
- Visceral pain from colon and rectum: the mechanotransduction and biomechanics.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeProtease-activated receptor 2 (PAR2) is expressed on nociceptive neurons, and can sensitize transient receptor potential (TRP) ion channels to amplify neurogenic inflammation and pain. The mechanisms by which this occurs are not fully understood. PAR2 causes receptor-operated activation of TRPV4 channels and TRPV4 null mice have attenuated PAR2-stimulated neurogenic inflammation and mechanical hyperalgesia. Here we investigate the intracellular signalling mechanisms underlying PAR2-induced TRPV4 channel activation and pain. EXPERIMENTAL APPROACH: Responses of non-transfected and TRPV4-transfected HEK293 cells to agonists of PAR2 (trypsin and SLIGRL) and TRPV4 channels (GSK1016790A) were determined using calcium imaging. Inhibitors of TRPV4 channels (HC067047), sarcoendoplasmic reticulum calcium transport ATPase (thapsigargin), Gαq (UBO-QIC), tyrosine kinases (bafetinib and dasatinib) or PI3 kinases (wortmannin and LY294002) were used to investigate signalling mechanisms. In vivo effects of tyrosine kinase inhibitors on PAR2 -induced mechanical hyperalgesia were assessed in mice. KEY
resultsIn non-transfected HEK293 cells, PAR2 activation transiently increased intracellular calcium ([Ca(2+) ]i ). Functional expression of TRPV4 channels caused a sustained increase of [Ca(2+) ]i , inhibited by HC067047, bafetinib and wortmannin; but not by thapsigargin, UBO-QIC, dasatinib or LY294002. Bafetinib but not dasatinib inhibited PAR2-induced mechanical hyperalgesia in vivo. CONCLUSIONS AND IMPLICATIONS: This study supports a role for tyrosine kinases in PAR2-mediated receptor-operated gating of TRPV4 channels, independent of Gαq stimulation. The ability of a tyrosine kinase inhibitor to diminish PAR2-induced activation of TRPV4 channels and consequent mechanical hyperalgesia identifies bafetinib (which is in development in oncology) as a potential novel analgesic therapy.
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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.