Pregnancy-induced decrease in the relaxant effect of terbutaline in the late-pregnant rat myometrium: role of G-protein activation and progesterone

Abstract

The effectiveness of b 2 -agonists in preterm delivery is reduced by several factors. The aim of this study was to determine the influence of late pregnancy in the uterus-relaxing effect of terbutaline in the rat in vitro. Rat uterine tissues from late pregnancy (days 15, 18, 20 and 22) were used. In vitro electrical field-stimulation (EFS) was used to evoke contractions. The radioligand-binding technique, reverse transcription-polymerase chain reaction and radioimmunoassay technique were used to determine the b-adrenergic receptor density and mRNA level and the plasma sex hormone level, respectively. The activated G-protein level of the b-adrenergic receptors was investigated by a radiolabelled GTP binding assay. EFS-induced contractions were inhibited by terbutaline. This effect decreased towards term with respect to both the EC 50 and maximal inhibition values. A drop in plasma progesterone level was also detected. Binding studies revealed an increase in b-adrenergic receptor number on the last day of pregnancy, which correlated with the change in receptor mRNA level. The G-protein-activating effect of terbutaline decreased continuously between days 15 and 20. Surprisingly, terbutaline decreased the G-protein activation to below the basal level on day 22. However, progesterone pretreatment set back the uterine action of terbutaline, increased the density of the b 2 -adrenergic receptors and their mRNA level and increased the G-proteinactivating property of terbutaline. These data provide evidence of a pregnancy-induced decrease in activated G-protein level after b 2 -agonist stimulation. The decrease in plasma progesterone level has a crucial role in this process. The effects of b 2 -adrenergic receptor agonists in tocolytic therapy may possibly be potentiated with progesterone.

Inhibitory effect of alprostadil against sevoflurane-induced myometrial relaxation in rats

“…Previous studies have found that sevofl urane reduces both the amplitude and frequency of myometrium contractions in myometrium isolated from humans [9,10] and rats [11,12]. Sevofl urane-induced myometrial relaxation has also been established using the AUC [13][14][15]. The failure to detect myometrial relaxation induced by sevofl urane via the amplitude or frequency in our study may be attributable to the small number of strips used.…”

“…The amplitude and frequency have traditionally been used as an index of myometrium contraction because they can be easily measured from analog data. Recently, new computer software has made it possible to calculate the AUC [13][14][15]. Previous studies have found that sevofl urane reduces both the amplitude and frequency of myometrium contractions in myometrium isolated from humans [9,10] and rats [11,12].…”

Uterus-Relaxing Study of a Sudanese Herb (El-Hazha)

“…Although (Gaspar et al, 2005) found on the late stage of pregnancy the sensitivity of the uterus to β-adrenergic activity was weaker than the non-pregnant, unfortunately the progesterone treatment did not potentiate the β-receptors sensitivity to this fraction, these findings can be explained by that, the β-ADR only partially participated in this relaxation besides other possible mechanism(s) or may be hide by the presence of other compounds in this semi-purified fraction.…”

“…In spite that on this stage of pregnancy the sensitivity of the uterus to β-adrenergic activity was weaker than the non pregnant (Gaspar et al, 2005).…”

Obesity in pregnancy: a novel concept on the roles of adipokines in uterine contractility

“…Estrogen enhances, while progesterone reduces the ability to contract (20). It was proved that the high plasma level of progesterone restores the function of β 2 -adrenergic receptors at the end of pregnancy (21). On the other hand, progesterone has anti-inflammatory effect that may have high physiological and therapeutic importance in the inflammatory approach to PD (22).…”