Kinsella, J.A., Debant, M., Parsonage, G. et al. (5 more authors) (2024) Pharmacology of PIEZO1 channels. British Journal of Pharmacology, 181 (23). pp. 4714-4732. ISSN 0007-1188
Abstract
PIEZO1 is a eukaryotic membrane protein that assembles as trimers to form calcium-permeable, non-selective cation channels with exquisite capabilities for mechanical force sensing and transduction of force into effect in diverse cell types that include blood cells, endothelial cells, epithelial cells, fibroblasts and stem cells and diverse systems that include bone, lymphatics and muscle. The channel has wide-ranging roles and is considered as a target for novel therapeutics in ailments spanning cancers and cardiovascular, dental, gastrointestinal, hepatobiliary, infectious, musculoskeletal, nervous system, ocular, pregnancy, renal, respiratory and urological disorders. The identification of PIEZO1 modulators is in its infancy but useful experimental tools emerged for activating, and to a lesser extent inhibiting, the channels. Elementary structure–activity relationships are known for the Yoda series of small molecule agonists, which show the potential for diverse physicochemical and pharmacological properties. Intriguing effects of Yoda1 include the stimulated removal of excess cerebrospinal fluid. Despite PIEZO1's broad expression, opportunities are suggested for selective positive or negative modulation without intolerable adverse effects. Here we provide a focused, non-systematic, narrative review of progress with this pharmacology and discuss potential future directions for research in the area.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | calcium ion; ion channel; mechanical force; non-selective cation channel; pharmacology; pressure; shear stress; small molecule modulator |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number British Heart Foundation RG/17/11/33042 Wellcome Trust 110044/Z/15/Z British Heart Foundation FS/19/59/34896 |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Sep 2024 11:41 |
Last Modified: | 11 Dec 2024 15:12 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/bph.17351 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:216824 |
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