ArticleThe Journal of general physiology2016
Carbenoxolone inhibits Pannexin1 channels through interactions in the first extracellular loop.
Article in The Journal of general physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 98 citations in OpenAlex.
- Discovery of membrane channel modulators via DNA encoded library screening using native like membrane protein nanoparticles.Scientific reports · 2026Article
- Pannexins in the heart: cell-specific expression and contributions to disease.Cell and tissue research · 2026Review
- Gap junction communication regulates luminal-myoepithelial crosstalk and cell differentiation in a bilayered human mammary epithelial cell model.Biology methods & protocols · 2026Article
- Gap Junctional Versus Paracrine Signaling in the Human Lens Epithelium: Analysis Based on Multicellular Ca²⁺ Imaging and Computational Modeling.Investigative ophthalmology & visual science · 2025Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- A metastasis-associated pannexin-1 mutant (Panx1The FEBS journal · 2025Article
- Mycobacterial Phenolic Glycolipid Triggers ATP-Mediated Neuronal P2X3 Signaling and Cough.bioRxiv : the preprint server for biology · 2025Article
- Article
- Pannexin 1 crosstalk with the Hippo pathway in malignant melanoma.The FEBS journal · 2025Article
- Novel Naphthyridones Targeting Pannexin 1 for Colitis Management.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dual Regulatory Roles of Pannexin 1 in the Pathogenesis and Recovery of Sepsis-Induced Acute Lung Injury.Infection and drug resistance · 2025Review
- Pannexin channels in inflammation and tumorigenesis.Frontiers in cell and developmental biology · 2025Review
- Pannexin 1 crosstalk with the Hippo pathway in malignant melanoma.bioRxiv : the preprint server for biology · 2024Article
- Cardiomyocyte PANX1 Controls Glycolysis and Neutrophil Recruitment in Hypertrophy.Circulation research · 2024Article
- Adenosine triphosphate release inhibitors targeting pannexin1 improve recovery after spinal cord injury.Nagoya journal of medical science · 2024Article
- Pannexins in the musculoskeletal system: new targets for development and disease progression.Bone research · 2024Review
- Cryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms.Nature communications · 2024Article
- Age-Dependent Activation of Purinergic Transmission Contributes to the Development of Epileptogenesis in ADSHE Model Rats.Biomolecules · 2024Article
- Review
- Age-Dependent Activation of Pannexin1 Function Contributes to the Development of Epileptogenesis in Autosomal Dominant Sleep-related Hypermotor Epilepsy Model Rats.International journal of molecular sciences · 2024Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Pannexin1 (Panx1) is an ATP release channel important for controlling immune responses and synaptic strength. Various stimuli including C-terminal cleavage, a high concentration of extracellular potassium, and voltage have been demonstrated to activate Panx1. However, it remains unclear how Panx1 senses and integrates such diverse stimuli to form an open channel. To provide a clue on the mechanism underlying Panx1 channel gating, we investigated the action mechanism of carbenoxolone (CBX), the most commonly used small molecule for attenuating Panx1 function triggered by a wide range of stimuli. Using a chimeric approach, we discovered that CBX reverses its action polarity and potentiates the voltage-gated channel activity of Panx1 when W74 in the first extracellular loop is mutated to a nonaromatic residue. A systematic mutagenesis study revealed that conserved residues in this loop also play important roles in CBX function, potentially by mediating CBX binding. We extended our experiments to other Panx1 inhibitors such as probenecid and ATP, which also potentiate the voltage-gated channel activity of a Panx1 mutant at position 74. Notably, probenecid alone can activate this mutant at a resting membrane potential. These data suggest that CBX and other inhibitors, including probenecid, attenuate Panx1 channel activity through modulation of the first extracellular loop. Our experiments are the first step toward identifying a previously unknown mode of CBX action, which provide insight into the role of the first extracellular loop in Panx1 channel gating.
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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.