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Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin), independent to the Rho kinase and extracellular calcium pathways

Ageing is associated with deteriorating urinary bladder function and an increasing prevalence of disorders such as underactive bladder. There are suggestions that G protein-coupled receptor (GPCR) second messenger pathways are altered during ageing, rather than the receptor proteins themselves. The...

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Autores principales: Phelps, Charlotte, Chess-Williams, Russ, Moro, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593738/
https://www.ncbi.nlm.nih.gov/pubmed/37872186
http://dx.doi.org/10.1038/s41598-023-44916-8
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author Phelps, Charlotte
Chess-Williams, Russ
Moro, Christian
author_facet Phelps, Charlotte
Chess-Williams, Russ
Moro, Christian
author_sort Phelps, Charlotte
collection PubMed
description Ageing is associated with deteriorating urinary bladder function and an increasing prevalence of disorders such as underactive bladder. There are suggestions that G protein-coupled receptor (GPCR) second messenger pathways are altered during ageing, rather than the receptor proteins themselves. The aim of this study was to identify age-related variations in GPCR activation systems in urinary bladder smooth muscle (detrusor). Isolated porcine detrusor strips were mounted in organ baths and contractile responses induced by receptor agonists were assessed and compared between juvenile (6 months) and adult (2 years) animals. The effects of drugs disrupting intracellular calcium signalling were also studied. Adult tissue was far more sensitive to stimulation by 5-hydroxytryptamine (42% greater increase than juvenile), prostaglandin-E2 (26% greater increase), and angiotensin-II (39% greater increase), however less sensitive to histamine. Although nifedipine and Y-27632 impacted the contraction to all agonists, there were no significant differences between juvenile and adult detrusor. Impairment of IP3-mediated calcium release by 2-aminoethyl diphenylborinate had no effect on any contractile activity, except for neurokinin-A which inhibited both juvenile and adult detrusor, and prostaglandin-E2 which inhibited juvenile. Carbachol, histamine, 5-hydroxytryptamine, and angiotensin-II were not affected by the application of 2-aminoethyl diphenylborinate. In conclusion, the contractile responses to all the GPCR agonists involved extracellular calcium influx and calcium sensitisation, but for prostaglandin-E2 the dependence on calcium from intracellular sources was greater in the younger animals.
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spelling pubmed-105937382023-10-25 Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin), independent to the Rho kinase and extracellular calcium pathways Phelps, Charlotte Chess-Williams, Russ Moro, Christian Sci Rep Article Ageing is associated with deteriorating urinary bladder function and an increasing prevalence of disorders such as underactive bladder. There are suggestions that G protein-coupled receptor (GPCR) second messenger pathways are altered during ageing, rather than the receptor proteins themselves. The aim of this study was to identify age-related variations in GPCR activation systems in urinary bladder smooth muscle (detrusor). Isolated porcine detrusor strips were mounted in organ baths and contractile responses induced by receptor agonists were assessed and compared between juvenile (6 months) and adult (2 years) animals. The effects of drugs disrupting intracellular calcium signalling were also studied. Adult tissue was far more sensitive to stimulation by 5-hydroxytryptamine (42% greater increase than juvenile), prostaglandin-E2 (26% greater increase), and angiotensin-II (39% greater increase), however less sensitive to histamine. Although nifedipine and Y-27632 impacted the contraction to all agonists, there were no significant differences between juvenile and adult detrusor. Impairment of IP3-mediated calcium release by 2-aminoethyl diphenylborinate had no effect on any contractile activity, except for neurokinin-A which inhibited both juvenile and adult detrusor, and prostaglandin-E2 which inhibited juvenile. Carbachol, histamine, 5-hydroxytryptamine, and angiotensin-II were not affected by the application of 2-aminoethyl diphenylborinate. In conclusion, the contractile responses to all the GPCR agonists involved extracellular calcium influx and calcium sensitisation, but for prostaglandin-E2 the dependence on calcium from intracellular sources was greater in the younger animals. Nature Publishing Group UK 2023-10-23 /pmc/articles/PMC10593738/ /pubmed/37872186 http://dx.doi.org/10.1038/s41598-023-44916-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 Article
Phelps, Charlotte
Chess-Williams, Russ
Moro, Christian
Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin), independent to the Rho kinase and extracellular calcium pathways
title Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin), independent to the Rho kinase and extracellular calcium pathways
title_full Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin), independent to the Rho kinase and extracellular calcium pathways
title_fullStr Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin), independent to the Rho kinase and extracellular calcium pathways
title_full_unstemmed Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin), independent to the Rho kinase and extracellular calcium pathways
title_short Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin), independent to the Rho kinase and extracellular calcium pathways
title_sort ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-ht (serotonin), independent to the rho kinase and extracellular calcium pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593738/
https://www.ncbi.nlm.nih.gov/pubmed/37872186
http://dx.doi.org/10.1038/s41598-023-44916-8
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