Progesterone decreases the relaxing effect of the β3-adrenergic receptor agonist BRL 37344 in the pregnant rat myometrium

Abstract

Although the published results regarding the function of the b 3 -adrenergic receptors (b 3 -ARs) in the regulation of smooth muscle activity are very promising, the question of the mechanism of b 3 -ARs' action in the pregnant myometrium cannot be fully answered by human investigations. To assess whether it possesses an essential role in the regulation of uterine contractility in pregnant rats, as in humans, we performed functional, western blotting and molecular biology experiments on the late-pregnant rat myometrium. The influence of progesterone on the function of the b 3 -ARs was also investigated. We demonstrated the presence and the functional activity of the b 3 -ARs in the late-pregnant rat myometrium. The maximum dose-dependent uterus-relaxing effect of the selective b 3 -agonist BRL 37344 was recorded at the end of pregnancy in rats, similarly as in humans. The extent of its relaxing action was regarded as moderate. The expression of b 3 -AR protein and mRNA remained unchanged during the investigated period. The administration of progesterone had no effect on the b 3 -AR mRNA and protein expression or the maximum relaxation effect of BRL 37344, but shifted the dose-response curve to the right and decreased the synthesis of the second messenger, cAMP. It can be concluded that the b 3 -ARs play an additional role in the regulation of the contractile activity of the pregnant rat uterus. The inhibitory effect of progesterone on the functional activity of the b 3 -ARs may have important consequences in the case of human application if this effect is also demonstrated in pregnant human myometrial tissue.

Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice

“…Several studies demonstrated that progesterone promotes myometrial relaxation. [43][44][45] Our finding that the absence of C5aR prevents PTD in the mouse models has important therapeutic implications. Blocking the complement cascade at C5a and CaR interaction inhibits mediators and effectors of cervical remodeling and prevents PTD, suggesting that complement might be a good target for therapy in women with PTD.…”

Role of beta-adrenergic receptor subtypes in pig uterus contractility with inflammation

“…With reference to the participation of NA in the contractility of healthy uteri, it is known that in various species this neurotransmitter stimulates (via α-ARs) and inhibit (via β-ARs) myometrial contractile activity 18 – 21 . Moreover, the role of β2- and β3-ARs in relaxation of human 22 , 23 , rat 24 , 25 and pig 26 , 27 MYO was indicated. In mice, the decrease in uterine contractility is mediated by β1- and β3-ARs 28 , 29 .…”

Influence of β2- and β3-adrenoceptor agonists on contractile activity of the porcine myometrium in the luteal phase and the first days of pregnancy

“…It was initially believed that β 2 -adrenoceptors play a predominant role in the relaxation of rat (Engstrom et al 1997) and human (Liu et al 1998) myometrium. However, the presence of functional β 3 -adrenoceptors has been demonstrated in human near-term (Bardou et al 2000) and non-pregnant myometrium (Rouget et al 2005) as well as in the myometrium of pregnant rats (Minorics et al 2009) and mice (Parida et al 2013). This may suggest a predominant role of the β 3 -adrenoceptor in human myometrium contractility (Rouget et al 2005, Ursino et al 2009).…”

“…ritodrine and salbutamol, are used clinically in the treatment of pre-term labour (de Heus et al 2009, Motazedian et al 2010, Parida et al 2013. Recently, an increased interest in the role of β 3 -adrenoceptors in the regulation of myometrium contractile activity in humans (Bardou et al 2000, Dennedy et al 2001, Rouget et al 2005, Pędzińska-Betiuk et al 2011, rats (Yurtcu et al 2006, Clouse et al 2007, Minorics et al 2009) and mice (Parida et al 2013) has been observed. The above studies have demonstrated the species variability of β 3 -adrenoceptor pharmacology, as well as the heterogeneous responsiveness to β 3 -adrenoceptor stimulation.…”