Altered levels of mRNA expression and pharmacological reactivity of alpha(1)-adrenergic receptor subtypes in the late-pregnant rat myometrium

摘要

The adrenergic system plays a major role in the regulation of the uterine contractility during pregnancy. Our previous studies have shown the significance of the alpha(1)-adrenergic receptors (ARs) in the control of pregnant uterine contractility both in vitro and in vivo. Our present aim was to determine the changes in mRNA expression and pharmacological reactivity of the alpha(1)-ARs on days 18, 20, and 22 of pregnancy. To demonstrate the expressions of alpha(1)-AR subtype mRNA, we used a reverse transcription-polymerase chain reaction (RT-PCR); the pharmacological reactivity was tested by electric field stimulation (EFS). The expression of alpha(1A)-AR mRNA increased from day 18 to 22, while no alpha(1B)-AR mRNA was detectable. We found a small increase in the expression of alpha(1D)-AR mRNA on day 20, which was not followed by a significant change in pharmacological reactivity. The alpha(1D)-receptor expression and pharmacological reactivity decreased significantly up to day 22. EFS studies revealed that the alpha(1A)-AR antagonist 5-methylurapidil had EC50 values (1.9 x 10(-6)-6.3 x 10(-6) M) about one order of magnitude lower than those of the alpha(1D)-AR antagonist BMY 7378 (4 x 10(-6)-3.6 x 10(-5) M). However, the a1B-AR antagonist cyclazosine exerted only a slight effect on the stimulated contractions. Strong correlations were found between the alpha(1A)-mRNA expression and the EC50 of 5-methylurapidil (r(2)=0.9712), and between the alpha(1D)-AR mRNA expression and the EC50 of BMY 7378 (r(2)=0.9937). Our findings suggest that both alpha(1A)- and alpha(1D)-ARs are involved in the regulation of the pregnant uterine contractility. The density and pharmacological reactivity indicate that the alpha(1A)-AR seems to play the major role in late-pregnant myometrial contraction. [References: 21]