Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling.
Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling.
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DOI：
10.1038/s41598-018-30094-5
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发表时间：
2018-08-03
影响因子：
4.6
通讯作者：
Obukhov AG
中科院分区：
文献类型：
--
作者：
Chen X;Meroueh M;Mazur G;Rouse E;Hundal KS;Stamatkin CW;Obukhov AG
调节子宫收缩力是妇女健康的一个重要方面。苯肾上腺素是一种α1肾上腺素受体的选择性激动剂和一种强效平滑肌收缩剂，广泛用于女性，甚至在妊娠期间也可用于缓解感冒相关症状、治疗产后痔疮和常规眼科检查。采用等长收缩张力记录法研究苯肾上腺素对小鼠子宫收缩力的影响。苯乙哌啶可降低非妊娠小鼠子宫环和子宫条的自发性和催产素诱导的收缩，IC 50约为1 μM。α1肾上腺素能受体抑制剂哌唑嗪不能阻止苯肾上腺素介导的舒张作用。相反，β2-肾上腺素受体拮抗剂ICI 118551抑制苯肾上腺素的舒张。在存在ICI 118551的情况下，高浓度（>30 μM）的苯肾上腺素引起小鼠子宫收缩，表明β-肾上腺素受体介导的抑制干扰了苯肾上腺素收缩电位。妊娠小鼠子宫中苯肾上腺素依赖性舒张减少。我们使用原代小鼠和人子宫平滑肌细胞（M/HUSMC）来建立潜在的机制。苯丙氨酸刺激M/HUSMCs细胞内cAMP的大量增加。当在雌激素和孕激素存在下培养HUSMCs以模拟妊娠环境时，这些cAMP瞬变减少。因此，苯肾上腺素在非妊娠小鼠子宫中是一种强松弛剂，但在妊娠子宫中表现出减弱的作用。
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.
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影响因子：
3.7
作者：
Herington JL;Swale DR;Brown N;Shelton EL;Choi H;Williams CH;Hong CC;Paria BC;Denton JS;Reese J
通讯作者：
Reese J
DOI：
10.1074/jbc.m110.197202
发表时间：
2011-02-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chen Q;Zhang Y;Peng H;Lei L;Kuang H;Zhang L;Ning L;Cao Y;Duan E
通讯作者：
Duan E
影响因子：
1.7
作者：
Anderson, Brian J.;Christensen, Lisa K.;Friesen, Robert H.
通讯作者：
Friesen, Robert H.
影响因子：
3.7
作者：
Chen X;Li W;Hiett SC;Obukhov AG
通讯作者：
Obukhov AG
DOI：
10.1111/j.1749-6632.2001.tb03804.x
发表时间：
2001-01-01
期刊：
HUMAN FERTILITY AND REPRODUCTION: THE OOCYTE, THE EMBRYO, AND THE UTERUS
影响因子：
--
作者：
Challis, JRG;Lye, SJ;Alfaidy, N
通讯作者：
Alfaidy, N