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Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria
Cantharidin, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), is known to increase the force of contraction and shorten the time to relaxation in human ventricular preparations. We hypothesized that cantharidin has similar positive inotropic effects in human right atria...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497697/ https://www.ncbi.nlm.nih.gov/pubmed/37097333 http://dx.doi.org/10.1007/s00210-023-02483-9 |
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author | Schwarz, R. Hofmann, B. Gergs, U. Neumann, J. |
author_facet | Schwarz, R. Hofmann, B. Gergs, U. Neumann, J. |
author_sort | Schwarz, R. |
collection | PubMed |
description | Cantharidin, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), is known to increase the force of contraction and shorten the time to relaxation in human ventricular preparations. We hypothesized that cantharidin has similar positive inotropic effects in human right atrial appendage (RAA) preparations. RAA were obtained during bypass surgery performed on human patients. These trabeculae were mounted in organ baths and electrically stimulated at 1 Hz. For comparison, we studied isolated electrically stimulated left atrial (LA) preparations and isolated spontaneously beating right atrial (RA) preparations from wild-type mice. Cumulatively applied (starting at 10 to 30 µM), cantharidin exerted a positive concentration-dependent inotropic effect that plateaued at 300 µM in the RAA, LA, and RA preparations. This positive inotropic effect was accompanied by a shortening of the time to relaxation in human atrial preparations (HAPs). Notably, cantharidin did not alter the beating rate in the RA preparations. Furthermore, cantharidin (100 µM) increased the phosphorylation state of phospholamban and the inhibitory subunit of troponin I in RAA preparations, which may account for the faster relaxation observed. The generated data indicate that PP1 and/or PP2A play a functional role in human atrial contractility. |
format | Online Article Text |
id | pubmed-10497697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-104976972023-09-14 Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria Schwarz, R. Hofmann, B. Gergs, U. Neumann, J. Naunyn Schmiedebergs Arch Pharmacol Research Cantharidin, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), is known to increase the force of contraction and shorten the time to relaxation in human ventricular preparations. We hypothesized that cantharidin has similar positive inotropic effects in human right atrial appendage (RAA) preparations. RAA were obtained during bypass surgery performed on human patients. These trabeculae were mounted in organ baths and electrically stimulated at 1 Hz. For comparison, we studied isolated electrically stimulated left atrial (LA) preparations and isolated spontaneously beating right atrial (RA) preparations from wild-type mice. Cumulatively applied (starting at 10 to 30 µM), cantharidin exerted a positive concentration-dependent inotropic effect that plateaued at 300 µM in the RAA, LA, and RA preparations. This positive inotropic effect was accompanied by a shortening of the time to relaxation in human atrial preparations (HAPs). Notably, cantharidin did not alter the beating rate in the RA preparations. Furthermore, cantharidin (100 µM) increased the phosphorylation state of phospholamban and the inhibitory subunit of troponin I in RAA preparations, which may account for the faster relaxation observed. The generated data indicate that PP1 and/or PP2A play a functional role in human atrial contractility. Springer Berlin Heidelberg 2023-04-25 2023 /pmc/articles/PMC10497697/ /pubmed/37097333 http://dx.doi.org/10.1007/s00210-023-02483-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Schwarz, R. Hofmann, B. Gergs, U. Neumann, J. Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria |
title | Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria |
title_full | Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria |
title_fullStr | Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria |
title_full_unstemmed | Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria |
title_short | Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria |
title_sort | cantharidin increases the force of contraction and protein phosphorylation in isolated human atria |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497697/ https://www.ncbi.nlm.nih.gov/pubmed/37097333 http://dx.doi.org/10.1007/s00210-023-02483-9 |
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