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Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling

Regulation of uterine contractility is an important aspect of women’s health. Phenylephrine, a selective agonist of the α(1)-adrenoceptor and a potent smooth muscle constrictor, is widely used in women even during pregnancy to relieve cold-related symptoms, to treat postpartum haemorrhoid, and durin...

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Autores principales: Chen, Xingjuan, Meroueh, Marya, Mazur, Gabriela, Rouse, Evan, Hundal, Karmjot Singh, Stamatkin, Christopher W., Obukhov, Alexander G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076280/
https://www.ncbi.nlm.nih.gov/pubmed/30076382
http://dx.doi.org/10.1038/s41598-018-30094-5
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author Chen, Xingjuan
Meroueh, Marya
Mazur, Gabriela
Rouse, Evan
Hundal, Karmjot Singh
Stamatkin, Christopher W.
Obukhov, Alexander G.
author_facet Chen, Xingjuan
Meroueh, Marya
Mazur, Gabriela
Rouse, Evan
Hundal, Karmjot Singh
Stamatkin, Christopher W.
Obukhov, Alexander G.
author_sort Chen, Xingjuan
collection PubMed
description Regulation of uterine contractility is an important aspect of women’s health. Phenylephrine, a selective agonist of the α(1)-adrenoceptor and a potent smooth muscle constrictor, is widely used in women even during pregnancy to relieve cold-related symptoms, to treat postpartum haemorrhoid, and during routine eye exams. We performed isometric tension recordings to investigate the effect of phenylephrine on mouse uterine contractility. Phenylephrine decreased spontaneous and oxytocin-induced contractions in non-pregnant mouse uterine rings and strips with an IC(50) of ~1 μM. Prazosin, an inhibitor of α(1)-adrenoceptor, did not prevent phenylephrine-mediated relaxations. Conversely, ICI118551, an antagonist of β2-adrenoceptors, inhibited phenylephrine relaxation. In the presence of ICI118551, high concentrations (>30 μM) of phenylephrine caused mouse uterine contractions, suggesting that β-adrenoceptor-mediated inhibition interferes with the phenylephrine contractile potential. Phenylephrine-dependent relaxation was reduced in the uterus of pregnant mice. We used primary mouse and human uterine smooth muscle cells (M/HUSMC) to establish the underlying mechanisms. Phenylephrine stimulated large increases in intracellular cAMP in M/HUSMCs. These cAMP transients were decreased when HUSMCs were cultured in the presence of oestrogen and progesterone to mimic the pregnancy milieu. Thus, phenylephrine is a strong relaxant in the non-pregnant mouse uterus, but exhibits diminished effect in the pregnant uterus.
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spelling pubmed-60762802018-08-07 Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling Chen, Xingjuan Meroueh, Marya Mazur, Gabriela Rouse, Evan Hundal, Karmjot Singh Stamatkin, Christopher W. Obukhov, Alexander G. Sci Rep Article Regulation of uterine contractility is an important aspect of women’s health. Phenylephrine, a selective agonist of the α(1)-adrenoceptor and a potent smooth muscle constrictor, is widely used in women even during pregnancy to relieve cold-related symptoms, to treat postpartum haemorrhoid, and during routine eye exams. We performed isometric tension recordings to investigate the effect of phenylephrine on mouse uterine contractility. Phenylephrine decreased spontaneous and oxytocin-induced contractions in non-pregnant mouse uterine rings and strips with an IC(50) of ~1 μM. Prazosin, an inhibitor of α(1)-adrenoceptor, did not prevent phenylephrine-mediated relaxations. Conversely, ICI118551, an antagonist of β2-adrenoceptors, inhibited phenylephrine relaxation. In the presence of ICI118551, high concentrations (>30 μM) of phenylephrine caused mouse uterine contractions, suggesting that β-adrenoceptor-mediated inhibition interferes with the phenylephrine contractile potential. Phenylephrine-dependent relaxation was reduced in the uterus of pregnant mice. We used primary mouse and human uterine smooth muscle cells (M/HUSMC) to establish the underlying mechanisms. Phenylephrine stimulated large increases in intracellular cAMP in M/HUSMCs. These cAMP transients were decreased when HUSMCs were cultured in the presence of oestrogen and progesterone to mimic the pregnancy milieu. Thus, phenylephrine is a strong relaxant in the non-pregnant mouse uterus, but exhibits diminished effect in the pregnant uterus. Nature Publishing Group UK 2018-08-03 /pmc/articles/PMC6076280/ /pubmed/30076382 http://dx.doi.org/10.1038/s41598-018-30094-5 Text en © The Author(s) 2018 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Xingjuan
Meroueh, Marya
Mazur, Gabriela
Rouse, Evan
Hundal, Karmjot Singh
Stamatkin, Christopher W.
Obukhov, Alexander G.
Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling
title Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling
title_full Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling
title_fullStr Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling
title_full_unstemmed Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling
title_short Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling
title_sort phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through camp signalling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076280/
https://www.ncbi.nlm.nih.gov/pubmed/30076382
http://dx.doi.org/10.1038/s41598-018-30094-5
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