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cAMP Compartmentalisation in Human Myometrial Cells

Preterm birth is the leading cause of childhood mortality and morbidity. A better understanding of the processes that drive the onset of human labour is essential to reduce the adverse perinatal outcomes associated with dysfunctional labour. Beta-mimetics, which activate the myometrial cyclic adenos...

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Autores principales: Varley, Alice, Koschinski, Andreas, Johnson, Mark R., Zaccolo, Manuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10001376/
https://www.ncbi.nlm.nih.gov/pubmed/36899855
http://dx.doi.org/10.3390/cells12050718
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author Varley, Alice
Koschinski, Andreas
Johnson, Mark R.
Zaccolo, Manuela
author_facet Varley, Alice
Koschinski, Andreas
Johnson, Mark R.
Zaccolo, Manuela
author_sort Varley, Alice
collection PubMed
description Preterm birth is the leading cause of childhood mortality and morbidity. A better understanding of the processes that drive the onset of human labour is essential to reduce the adverse perinatal outcomes associated with dysfunctional labour. Beta-mimetics, which activate the myometrial cyclic adenosine monophosphate (cAMP) system, successfully delay preterm labour, suggesting a key role for cAMP in the control of myometrial contractility; however, the mechanisms underpinning this regulation are incompletely understood. Here we used genetically encoded cAMP reporters to investigate cAMP signalling in human myometrial smooth muscle cells at the subcellular level. We found significant differences in the dynamics of the cAMP response in the cytosol and at the plasmalemma upon stimulation with catecholamines or prostaglandins, indicating compartment-specific handling of cAMP signals. Our analysis uncovered significant disparities in the amplitude, kinetics, and regulation of cAMP signals in primary myometrial cells obtained from pregnant donors compared with a myometrial cell line and found marked response variability between donors. We also found that in vitro passaging of primary myometrial cells had a profound impact on cAMP signalling. Our findings highlight the importance of cell model choice and culture conditions when studying cAMP signalling in myometrial cells and we provide new insights into the spatial and temporal dynamics of cAMP in the human myometrium.
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spelling pubmed-100013762023-03-11 cAMP Compartmentalisation in Human Myometrial Cells Varley, Alice Koschinski, Andreas Johnson, Mark R. Zaccolo, Manuela Cells Article Preterm birth is the leading cause of childhood mortality and morbidity. A better understanding of the processes that drive the onset of human labour is essential to reduce the adverse perinatal outcomes associated with dysfunctional labour. Beta-mimetics, which activate the myometrial cyclic adenosine monophosphate (cAMP) system, successfully delay preterm labour, suggesting a key role for cAMP in the control of myometrial contractility; however, the mechanisms underpinning this regulation are incompletely understood. Here we used genetically encoded cAMP reporters to investigate cAMP signalling in human myometrial smooth muscle cells at the subcellular level. We found significant differences in the dynamics of the cAMP response in the cytosol and at the plasmalemma upon stimulation with catecholamines or prostaglandins, indicating compartment-specific handling of cAMP signals. Our analysis uncovered significant disparities in the amplitude, kinetics, and regulation of cAMP signals in primary myometrial cells obtained from pregnant donors compared with a myometrial cell line and found marked response variability between donors. We also found that in vitro passaging of primary myometrial cells had a profound impact on cAMP signalling. Our findings highlight the importance of cell model choice and culture conditions when studying cAMP signalling in myometrial cells and we provide new insights into the spatial and temporal dynamics of cAMP in the human myometrium. MDPI 2023-02-24 /pmc/articles/PMC10001376/ /pubmed/36899855 http://dx.doi.org/10.3390/cells12050718 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Varley, Alice
Koschinski, Andreas
Johnson, Mark R.
Zaccolo, Manuela
cAMP Compartmentalisation in Human Myometrial Cells
title cAMP Compartmentalisation in Human Myometrial Cells
title_full cAMP Compartmentalisation in Human Myometrial Cells
title_fullStr cAMP Compartmentalisation in Human Myometrial Cells
title_full_unstemmed cAMP Compartmentalisation in Human Myometrial Cells
title_short cAMP Compartmentalisation in Human Myometrial Cells
title_sort camp compartmentalisation in human myometrial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10001376/
https://www.ncbi.nlm.nih.gov/pubmed/36899855
http://dx.doi.org/10.3390/cells12050718
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