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

Xingjuan Chen, Marya Meroueh, Gabriela Mazur, Evan Rouse, Karmjot Singh Hundal, Christopher W. Stamatkin, Alexander Obukhov

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Regulation of uterine contractility is an important aspect of women’s health. Phenylephrine, a selective agonist of the α1-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 IC50 of ~1 μM. Prazosin, an inhibitor of α1-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.

Original languageEnglish (US)
Article number11666
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Common Cold
Uterine Contraction
Phenylephrine
Adrenergic Receptors
Uterus
Hemorrhoids
Pregnancy
Myometrium
Prazosin
Women's Health
Oxytocin
Postpartum Period
Inhibitory Concentration 50
Smooth Muscle Myocytes
Progesterone
Smooth Muscle
Estrogens

ASJC Scopus subject areas

  • General

Cite this

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.

In: Scientific Reports, Vol. 8, No. 1, 11666, 01.12.2018.

Research output: Contribution to journalArticle

Chen, Xingjuan ; Meroueh, Marya ; Mazur, Gabriela ; Rouse, Evan ; Hundal, Karmjot Singh ; Stamatkin, Christopher W. ; Obukhov, Alexander. / Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{8296efe004e14dea8b46d494f42be1b8,
title = "Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling",
abstract = "Regulation of uterine contractility is an important aspect of women’s health. Phenylephrine, a selective agonist of the α1-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 IC50 of ~1 μM. Prazosin, an inhibitor of α1-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.",
author = "Xingjuan Chen and Marya Meroueh and Gabriela Mazur and Evan Rouse and Hundal, {Karmjot Singh} and Stamatkin, {Christopher W.} and Alexander Obukhov",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-30094-5",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling

AU - Chen, Xingjuan

AU - Meroueh, Marya

AU - Mazur, Gabriela

AU - Rouse, Evan

AU - Hundal, Karmjot Singh

AU - Stamatkin, Christopher W.

AU - Obukhov, Alexander

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Regulation of uterine contractility is an important aspect of women’s health. Phenylephrine, a selective agonist of the α1-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 IC50 of ~1 μM. Prazosin, an inhibitor of α1-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.

AB - Regulation of uterine contractility is an important aspect of women’s health. Phenylephrine, a selective agonist of the α1-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 IC50 of ~1 μM. Prazosin, an inhibitor of α1-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.

UR - http://www.scopus.com/inward/record.url?scp=85051064985&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051064985&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-30094-5

DO - 10.1038/s41598-018-30094-5

M3 - Article

C2 - 30076382

AN - SCOPUS:85051064985

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 11666

ER -