ArticleBritish journal of pharmacology2013
Control of TMEM16A by INO-4995 and other inositolphosphates.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- A Decade-Old Atlas of TMEM (Transmembrane) Protein Family in Lung Cancer: Lessons Learnt and Future Directions.International journal of molecular sciences · 2026Review
- Discovery of Fungus-Derived Nornidulin as a Novel TMEM16A Inhibitor: A Potential Therapy to Inhibit Mucus Secretion in Asthma.Journal of experimental pharmacology · 2023Article
- Rare Trafficking CFTR Mutations Involve Distinct Cellular Retention Machineries and Require Different Rescuing Strategies.International journal of molecular sciences · 2021Article
- Calmodulin-Dependent Regulation of Overexpressed but Not Endogenous TMEM16A Expressed in Airway Epithelial Cells.Membranes · 2021Article
- The CaActa pharmaceutica Sinica. B · 2021Review
- CLCA1 Regulates Airway Mucus Production and Ion Secretion Through TMEM16A.International journal of molecular sciences · 2021Article
- Pharmacological Modulation of Ion Channels for the Treatment of Cystic Fibrosis.Journal of experimental pharmacology · 2021Review
- Organoids as a personalized medicine tool for ultra-rare mutations in cystic fibrosis: The case of S955P and 1717-2A>G.Biochimica et biophysica acta. Molecular basis of disease · 2020Article
- Pharmacological Inhibition and Activation of the CaInternational journal of molecular sciences · 2020Article
- Review
- A network of phosphatidylinositol 4,5-bisphosphate binding sites regulates gating of the CaProceedings of the National Academy of Sciences of the United States of America · 2019Article
- The multifaceted role of TMEM16A in cancer.Cell calcium · 2019Review
- Niclosamide repurposed for the treatment of inflammatory airway disease.JCI insight · 2019Article
- TMEM16F/Anoctamin 6 in Ferroptotic Cell Death.Cancers · 2019Article
- Review
- TMEM16A in Cystic Fibrosis: Activating or Inhibiting?Frontiers in pharmacology · 2019Review
- Calcium-Activated ClInternational journal of molecular sciences · 2018Review
- The association between the expression of PAR2 and TMEM16A and neuropathic pain.Molecular medicine reports · 2018Article
- Regulation of TMEM16A/ANO1 and TMEM16F/ANO6 ion currents and phospholipid scrambling by CaThe Journal of physiology · 2018Article
- Cell-specific mechanisms of TMEM16A CaMolecular cancer · 2017Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeCa(2+)-dependent Cl(-) secretion (CaCC) in airways and other tissues is due to activation of the Cl(-) channel TMEM16A (anoctamin 1). Earlier studies suggested that Ca(2+) -activated Cl(-) channels are regulated by membrane lipid inositol phosphates, and that 1-O-octyl-2-O-butyryl-myo-inositol 3,4,5,6-tetrakisphosphate octakis(propionoxymethyl) ester (INO-4995) augments CaCC. Here we examined whether TMEM16A is the target for INO-4995 and if the channel is regulated by inositol phosphates. EXPERIMENTAL APPROACH: The effects of INO-4995 on CaCC were examined in overexpressing HEK293, colonic and primary airway epithelial cells as well as Xenopus oocytes. We used patch clamping, double electrode voltage clamp and Ussing chamber techniques. KEY
resultsWe found that INO-4995 directly activates a TMEM16A whole cell conductance of 6.1 ± 0.9 nS pF(-1) in overexpressing cells. The tetrakisphosphates Ins(3,4,5,6)P(4) or Ins(1,3,4,5)P(4) and enzymes controlling levels of InsP(4) or PIP(2) and PIP(3) had no effects on the magnitude or kinetics of TMEM16A currents. In contrast in Xenopus oocytes, human airways and colonic cells, which all express TMEM16A endogenously, Cl(-) currents were not acutely activated by INO-4995. However incubation with INO-4995 augmented 1.6- to 4-fold TMEM16A-dependent Cl(-) currents activated by ionomycin or ATP, while intracellular Ca(2+) signals were not affected. The potentiating effect of INO-4995 on transient ATP-activated TMEM16A-currents in cystic fibrosis (CF) airways was twice of that observed in non-CF airways. CONCLUSIONS AND IMPLICATIONS: These data indicate that TMEM16A is the target for INO-4995, although the mode of action appears different for overexpressed and endogenous channels. INO-4995 may be useful for the treatment of CF lung disease.
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