Altered levels of mRNA expression and pharmacological reactivity of α₁‐adrenergic receptor subtypes in the late‐pregnant rat myometrium

Abstract

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 alpha1-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 alpha1-ARs on days 18, 20, and 22 of pregnancy. To demonstrate the expressions of alpha1-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 alpha1A-AR mRNA increased from day 18 to 22, while no alpha1B-AR mRNA was detectable. We found a small increase in the expression of alpha1D-AR mRNA on day 20, which was not followed by a significant change in pharmacological reactivity. The alpha1D-receptor expression and pharmacological reactivity decreased significantly up to day 22. EFS studies revealed that the alpha1A-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 alpha1D-AR antagonist BMY 7378 (4 x 10(-6)-3.6 x 10(-5) M). However, the alpha1B-AR antagonist cyclazosine exerted only a slight effect on the stimulated contractions. Strong correlations were found between the alpha1A-mRNA expression and the EC50 of 5-methylurapidil (r(2) =0.9712), and between the alpha1D-AR mRNA expression and the EC50 of BMY 7378 (r(2) = 0.9937). Our findings suggest that both alpha1A- and alpha1D-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.

Role of Capsaicin-Sensitive Nerve Fibers in Uterine Contractility in the Rat1

“…Anatomical, neurochemical and pharmacological studies revealed that this may be attributed to the effects of neuropeptides released from stimulated sensory nerve terminals [8][9][10]. This particular local regulatory or sensory efferent function is a characteristic trait of primary afferent neurons that are specifically sensitive to 1 This work was supported by the Richter Gedeon Centennial Foundation. 2 Correspondence: George Falkay, Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Eö tvö s u.…”

“…The changes in adrenergic receptor density associated with an ongoing degeneration process in the course of pregnancy and their role in the modulation of uterine contractility is well established [1][2][3][4][5]. In most visceral organs, stimulation of sensory nerves may evoke significant alterations in smooth muscle contractile activity [6,7].…”

Increased potency of α1-adrenergic receptors to induce inositol phosphates production correlates with the up-regulation of α1d/Ghα/phospholipase Cδ1 signaling pathway in term rat myometrium

“…The three a1-AR subtypes (a1a, a1b, and a1d) are present during the second half of pregnancy although they exhibit different expression patterns. Previous studies attempted to assign different roles to a1-AR subtypes in the regulation of uterine contraction (Ducza et al 2002, Mihalyi et al 2003. It is, however, clear from the present study that, in physiological conditions where the three a1-AR subtypes are co-activated by their endogenous ligand norepinephrine, contraction of the circular muscle is induced at term but not as potently as does oxytocin.…”

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

“…To date, only limited information is available as concerns the existence of the b 3 -AR mRNA and protein in the latepregnant rat myometrium, or its pharmacological role in the regulation of uterine smooth muscle activity in the rat. Moreover, earlier experimental results are available on the pharmacological reactivity and receptor expression patterns of other adrenergic receptor subtypes (a 1 -, a 2 -and b 2 -ARs) in the pregnant rat myometrium (Ducza et al 2002, Gáspár et al 2005. If a comparison between the b 3 -and the other ARs is needed, it is necessary to have results from the same species.…”