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cAMP Compartmentalisation in Human Myometrial Cells.
Varley, Alice; Koschinski, Andreas; Johnson, Mark R; Zaccolo, Manuela.
Afiliação
  • Varley A; Department of Metabolism, Digestion and Reproduction, Imperial College London, Academic Department of Obstetrics & Gynaecology, Level 3, Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
  • Koschinski A; Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Sherrington Road, Oxford OX1 3PT, UK.
  • Johnson MR; Department of Metabolism, Digestion and Reproduction, Imperial College London, Academic Department of Obstetrics & Gynaecology, Level 3, Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
  • Zaccolo M; Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Sherrington Road, Oxford OX1 3PT, UK.
Cells ; 12(5)2023 02 24.
Article em En | MEDLINE | ID: mdl-36899855
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nascimento Prematuro / Miométrio Tipo de estudo: Prognostic_studies Limite: Female / Humans / Newborn / Pregnancy Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nascimento Prematuro / Miométrio Tipo de estudo: Prognostic_studies Limite: Female / Humans / Newborn / Pregnancy Idioma: En Ano de publicação: 2023 Tipo de documento: Article