ArticleBritish journal of pharmacology2016
Eact, a small molecule activator of TMEM16A, activates TRPV1 and elicits pain- and itch-related behaviours.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- An All-Optical Approach to Probe Chloride Transport with a Bright ChlorON.bioRxiv : the preprint server for biology · 2026Article
- Activation of anoctamin-1 calcium-activated chloride channels reduces voluntary alcohol consumption in rats.Neuropharmacology · 2025Article
- Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).Handbook of experimental pharmacology · 2024Article
- Activation of Calcium-Activated Chloride Channels Suppresses Inherited Seizure Susceptibility in Genetically Epilepsy-Prone Rats.Biomedicines · 2022Article
- Positive modulation of the TMEM16B mediated currents by TRPV4 antagonist.Biochemistry and biophysics reports · 2021Article
- The Role of TMEM16A/ERK/NK-1 Signaling in Dorsal Root Ganglia Neurons in the Development of Neuropathic Pain Induced by Spared Nerve Injury (SNI).Molecular neurobiology · 2021Article
- The CaActa pharmaceutica Sinica. B · 2021Review
- Pharmacological Modulation of Ion Channels for the Treatment of Cystic Fibrosis.Journal of experimental pharmacology · 2021Review
- TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis.American journal of respiratory and critical care medicine · 2020Article
- Pharmacological Inhibition and Activation of the CaInternational journal of molecular sciences · 2020Article
- Agonism of the TMEM16A calcium-activated chloride channel modulates airway smooth muscle tone.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Chloride - The Underrated Ion in Nociceptors.Frontiers in neuroscience · 2020Review
- The pharmacology of itch.British journal of pharmacology · 2019Article
- Drug Repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodilate Airways.Frontiers in pharmacology · 2019Article
- Optogenetic Induction of Colonic Motility in Mice.Gastroenterology · 2018Article
- Article
- Sensory TRP channels contribute differentially to skin inflammation and persistent itch.Nature communications · 2017Article
- Erratum.British journal of pharmacology · 2016Article
- Eact, a small molecule activator of TMEM16A, activates TRPV1 and elicits pain- and itch-related behaviours.British journal of pharmacology · 2016Article
Corrections and comments
- Erratum issuedErratum.2016
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
background and purposeTMEM16A, also known as anoctamin 1 channel, is a member of the Ca(2+)-activated chloride channels family and serves as a heat sensor in the primary nociceptors. Eact is a recently discovered small molecule activator of the TMEM16A channel. Here, we asked if Eact produces pain- and itch-related responses in vivo and investigated the cellular and molecular basis of Eact-elicited responses in dorsal root ganglia (DRG) neurons. EXPERIMENTAL APPROACH: We employed behavioural testing combined with pharmacological inhibition and genetic ablation approaches to identify transient receptor potential vanilloid 1 (TRPV1) as the prominent mediator for Eact-evoked itch- or pain-related responses. We investigated the effects of Eact on TRPV1 and TMEM16A channels expressed in HEK293T cells and in DRG neurons isolated from wild type and Trpv1(-/-) mice using Ca(2+) imaging and patch-clamp recordings. We also used site-directed mutagenesis to determine the molecular basis of Eact activation of TRPV1. KEY
resultsAdministration of Eact elicited both itch- and pain-related behaviours. Unexpectedly, the Eact-elicited behavioural responses were dependent on the function of TRPV1, as shown by pharmacological inhibition and genetic ablation studies. Eact activated membrane currents and increased intracellular free Ca(2+) in both TRPV1-expressing HEK293T cells and isolated DRG neurons in a TRPV1-dependent manner. Eact activation of the TRPV1 channel was severely attenuated by mutations disrupting the capsaicin-binding sites. CONCLUSIONS AND IMPLICATIONS: Our results suggest that Eact activates primary sensory nociceptors and produces both pain and itch responses mainly through direct activation of TRPV1 channels.
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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.