Review
Cell Biology
Christie Mitri, Himanshu Sharma, Harriet Corvol, Olivier Tabary
Summary: Cystic fibrosis is a common hereditary disease affecting Caucasians, with approximately 75,000 patients worldwide. Mutations in the CFTR gene cause dysfunction in the CFTR protein, and treatments include correctors and potentiators; however, alternative CFTR-independent strategies are still being explored.
Article
Medicine, Research & Experimental
Pengmei Guo, Yu Liu, Xiaojia Xu, Guijin Ma, Xiaomin Hou, Yanying Fan, Mingsheng Zhang
Summary: The study showed that enhanced activity of CaCCs in arterial smooth muscle cells and increased Ca2+ mobilization play a pivotal role in the distinctive hypercontractility of rat coronary arteries to acidosis, which may lead to a new approach in understanding and treating cardiac complications in severe acidosis.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Henry Danahay, Sarah Lilley, Kathryn Adley, Holly Charlton, Roy Fox, Martin Gosling
Summary: Niclosamide and benzbromarone have been considered as clinical candidates for the treatment of airway diseases due to their activity as inhibitors of the calcium activated chloride channel TMEM16A. However, this study reveals that both compounds have off-target effects and also questions the classification of niclosamide as a TMEM16A blocker. The study further suggests a potential role of TMEM16A in the regulation of epithelial ion transport and mucus secretion in the airway.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Luis J. Galietta
Summary: Cystic fibrosis is a genetic disease caused by the dysfunction of CFTR, a chloride channel expressed in epithelial cells. The loss of CFTR function leads to chronic bacterial infections and airway obstruction. Another chloride channel called TMEM16A may play a role in mucus hypersecretion, but further research is needed to confirm this relationship.
CURRENT OPINION IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Yani Liu, Zongtao Liu, KeWei Wang
Summary: ANO1 gene encodes a Ca2+ activated Cl- channel critical for physiological functions, with abnormal expression or dysfunction linked to various diseases. The lack of specific modulators hinders the validation of ANO1 as a therapeutic target.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Multidisciplinary Sciences
Andy K. M. Lam, Jan Rheinberger, Cristina Paulino, Raimund Dutzler
Summary: The study elucidated the conformational changes triggered by the binding of cytoplasmic Ca2+ to the TMEM16A channel and identified three hydrophobic residues as constituents of the channel gate. Mutations in these residues increase Ca2+ potency and result in basal activity, while an activating mutant shows a conformational change that contributes to Ca2+ binding and basal activity. Despite no physical contact, these residues functionally interact to stabilize the gate in the closed conformation, explaining the low open probability of the channel in the absence of Ca2+.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Rumaitha Al-Hosni, Zeki Ilkan, Emilio Agostinelli, Paolo Tammaro
Summary: This article critically analyzes recent developments in TMEM16A pharmacology and discusses the therapeutic opportunities provided by this target.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Ritu Dwivedi, Bernard T. Drumm, Tuleen Alkawadri, S. Lorraine Martin, Gerard P. Sergeant, Mark A. Hollywood, Keith D. Thornbury
Summary: We investigated the effects of TMEM16A blockers on isometric contractions in mouse bronchial rings and intracellular calcium in bronchial myocytes. We found that benzbromarone and MONNA caused intracellular calcium release, resulting in a reduction of carbachol-induced contractions.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
M. B. Hawn, E. Akin, H. C. Hartzell, I. A. Greenwood, N. Leblanc
Summary: This article summarizes the functions and regulatory mechanisms of Ca2+-activated Cl- channels, focusing on recent studies on ANO1 and its regulation by internal Ca2+, membrane lipids, and protein partners. It also reviews the basic properties, historical controversies, and molecular structures of CaCCs.
Article
Biochemistry & Molecular Biology
Andy K. M. Lam, Raimund Dutzler
Summary: In this study, the mechanism of agonist efficacy in the calcium-activated chloride channel TMEM16A was investigated. The researchers found that the conformation of the pore-lining helix alpha 6 around the Ca2+-binding site determines the agonist efficacy. The closure of the binding site is coupled to the opening of the inner pore gate, controlling the channel's open probability and conductance.
Article
Physiology
Lisa Ebihara, Pooja Acharya, Jun-Jie Tong
Summary: Our study demonstrates that mechanical stress can rapidly and reversibly modulate calcium-activated chloride channels (CaCCs) in the lens, suggesting their involvement in regulating volume in this organ. The activation and recovery of the flow-induced current occurs rapidly, similar to the time frame of accommodation. The flow-induced current is predominantly due to TMEM16A chloride channels and is not dependent on calcium influx through other mechanosensitive ion channels.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Maximilian L. Mager, Cosmin I. Ciotu, Markus Gold-Binder, Stefan Heber, Michael J. M. Fischer
Summary: Several preservatives commonly used in pharmaceuticals can activate the TRPA1 channel, especially when combined with proinflammatory mediators.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alejandro Mata-Daboin, Tessa A. C. Garrud, Carlos Fernandez-Pena, Dieniffer Peixoto-Neves, M. Dennis Leo, Angelica K. Bernardelli, Purnima Singh, Kafait U. Malik, Jonathan H. Jaggar
Summary: This study investigates the role of the TMEM16A channel in endothelial cells and its influence on blood pressure regulation. The activation of TMEM16A channels by vasodilators such as acetylcholine and TRPV4 leads to arterial hyperpolarization, vasodilation, and reduced blood pressure. Deficiency of TMEM16A channels in endothelial cells results in increased systemic blood pressure.
Article
Biochemistry & Molecular Biology
Hee-Jin Kim, Jeong-Yub Kim, Chan-Woong Jung, Young-Sun Lee, Joon-Yong An, Eun Ho Kim, Ki-Hong Kim, Sang Pyung Lee, Jae-Yong Park, Myung-Jin Park
Summary: ANO1 interacts with EGFRvIII, increases its protein stability, and supports the maintenance of stemness and tumor progression in GSCs; knockdown of ANO1 can suppress self-renewal and invasion activities in GSCs.
Article
Chemistry, Multidisciplinary
Joao Conde, Ruth A. Pumroy, Charlotte Baker, Tiago Rodrigues, Ana Guerreiro, Barbara B. Sousa, Marta C. Marques, Bernardo P. de Almeida, Sohyon Lee, Elvira P. Leites, Daniel Picard, Amrita Samanta, Sandra H. Vaz, Florian Sieglitz, Maike Langini, Marc Remke, Rafael Roque, Tobias Weiss, Michael Weller, Yuhang Liu, Seungil Han, Francisco Corzana, Vanessa A. Morais, Claudia C. Faria, Tania Carvalho, Panagis Filippakopoulos, Berend Snijder, Nuno L. Barbosa-Morais, Vera Y. Moiseenkova-Bell, Goncalo J. L. Bernardes
Summary: The study investigated the regulation of piperlongumine (PL) on the human transient receptor potential vanilloid 2 (hTRPV2) channel and its mechanism of action in combating glioblastoma. Experimental results demonstrated that PL affects the activity of hTRPV2 channel in a specific way, effectively reducing malignant cells in GBM tumors. Further research found that PL also exhibits selective cytotoxicity towards malignant cells in samples derived from GBM patients.
ACS CENTRAL SCIENCE
(2021)
Article
Pharmacology & Pharmacy
Nils J. G. Rorsman, Chau M. Ta, Hannah Garnett, Pawel Swietach, Paolo Tammaro
BRITISH JOURNAL OF PHARMACOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Oscar Moran, Alessandro Grottesi, Andrew J. Chadbum, Paolo Tammaro
BIOPHYSICAL CHEMISTRY
(2013)
Article
Ophthalmology
Adiv A. Johnson, Yong-Suk Lee, Andrew J. Chadburn, Paolo Tammaro, Forbes D. Manson, Lihua Y. Marmorstein, Alan D. Marmorstein
EXPERIMENTAL EYE RESEARCH
(2014)
Article
Neurosciences
Boris Manoury, Aiste Tamuleviciute, Paolo Tammaro
JOURNAL OF PHYSIOLOGY-LONDON
(2010)
Article
Neurosciences
Aiste Adomaviciene, Keith J. Smith, Hannah Garnett, Paolo Tammaro
JOURNAL OF PHYSIOLOGY-LONDON
(2013)
Article
Multidisciplinary Sciences
Nellie Y. Loh, Liz Bentley, Henrik Dimke, Sjoerd Verkaart, Paolo Tammaro, Caroline M. Gorvin, Michael J. Stechman, Bushra N. Ahmad, Fadil M. Hannan, Sian E. Piret, Holly Evans, Ilaria Bellantuono, Tertius A. Hough, William D. Fraser, Joost G. J. Hoenderop, Frances M. Ashcroft, Steve D. M. Brown, Rene J. M. Bindels, Roger D. Cox, Rajesh V. Thakker
Article
Multidisciplinary Sciences
K. Simon R. Bushell, Ashley C. W. Pike, Maria E. Falzone, Nils J. G. Rorsman, Chau M. Ta, Robin A. Corey, Thomas D. Newport, John C. Christianson, Lara F. Scofano, Chitra A. Shintre, Annamaria Tessitore, Amy Chu, Qinrui Wang, Leela Shrestha, Shubhashish M. M. Mukhopadhyay, James D. Love, Nicola A. Burgess-Brown, Rebecca Sitsapesan, Phillip J. Stansfeld, Juha T. Huiskonen, Paolo Tammaro, Alessio Accardi, Elisabeth P. Carpenter
NATURE COMMUNICATIONS
(2019)
Review
Biochemistry & Molecular Biology
Emilio Agostinelli, Paolo Tammaro
Summary: The TMEM16A/anoctamin-1 calcium-activated chloride channel plays a vital role in controlling vascular tone and epithelial ion transport. It is a founding member of a protein family with diverse functions, and its regulation is influenced by calcium signaling as well as various other cellular factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Chau M. Ta, Kathryn E. Acheson, Nils J. G. Rorsman, Remco C. Jongkind, Paolo Tammaro
BRITISH JOURNAL OF PHARMACOLOGY
(2017)