ArticleBiomolecules2019
Multiple Modulation of Acid-Sensing Ion Channel 1a by the Alkaloid Daurisoline.
Article in Biomolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Therapeutic Promise and Biotechnological Prospects ofInternational journal of molecular sciences · 2025Review
- Two Amino Acid Substitutions Improve the Pharmacological Profile of the Snake Venom Peptide Mambalgin.Toxins · 2025Article
- Daurisoline Inhibiting Tumor Angiogenesis and Epithelial-Mesenchymal Transition in Bladder Cancer by Mediating HAKAI Protein Stability.Iranian journal of pharmaceutical research : IJPR · 2022Article
- Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities.International journal of molecular sciences · 2022Review
- Molecular mechanism and structural basis of small-molecule modulation of the gating of acid-sensing ion channel 1.Communications biology · 2021Article
- New Insectotoxin from Tibellus Oblongus Spider Venom Presents Novel Adaptation of ICK Fold.Toxins · 2021Article
- The Role of ASIC1a in Epilepsy: A Potential Therapeutic Target.Current neuropharmacology · 2021Review
- Histidine Residues Are Responsible for Bidirectional Effects of Zinc on Acid-Sensing Ion Channel 1a/3 Heteromeric Channels.Biomolecules · 2020Article
- Sevanol and Its Analogues: Chemical Synthesis, Biological Effects and Molecular Docking.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Mambalgin-2 Induces Cell Cycle Arrest and Apoptosis in Glioma Cells via Interaction with ASIC1a.Cancers · 2020Article
- Animal, Herb, and Microbial Toxins for Structural and Pharmacological Study of Acid-Sensing Ion Channels.Frontiers in pharmacology · 2020Review
- Alkaloid Lindoldhamine Inhibits Acid-Sensing Ion Channel 1a and Reveals Anti-Inflammatory Properties.Toxins · 2019Article
- Endogenous Neuropeptide Nocistatin Is a Direct Agonist of Acid-Sensing Ion Channels (ASIC1, ASIC2 and ASIC3).Biomolecules · 2019Article
- ASIC1a Inhibitor mambalgin-2 Suppresses the Growth of Leukemia Cells by Cell Cycle Arrest.Acta naturaeArticle
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acid-sensing ion channels (ASICs) are proton-gated sodium-selective channels that are expressed in the peripheral and central nervous systems. ASIC1a is one of the most intensively studied isoforms due to its importance and wide representation in organisms, but it is still largely unexplored as a target for therapy. In this study, we demonstrated response of the ASIC1a to acidification in the presence of the daurisoline (DAU) ligand. DAU alone did not activate the channel, but in combination with protons, it produced the second peak component of the ASIC1a current. This second peak differs from the sustained component (which is induced by RF-amide peptides), as the second (DAU-induced) peak is completely desensitized, with the same kinetics as the main peak. The co-application of DAU and mambalgin-2 indicated that their binding sites do not overlap. Additionally, we found an asymmetry in the pH activation curve of the channel, which was well-described by a mathematical model based on the multiplied probabilities of protons binding with a pool of high-cooperative sites and a single proton binding with a non-cooperative site. In this model, DAU targeted the pool of high-cooperative sites and, when applied with protons, acted as an inhibitor of ASIC1a activation. Moreover, DAU's occupation of the same binding site most probably reverses the channel from steady-state desensitization in the pH 6.9-7.3 range. DAU features disclose new opportunities in studies of ASIC structure and function.
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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.