Yurtcu Nazan, Cetin Ali, Karadas Baris, Gonca Imir Ayse, Kaya Tijen, Erselcan Taner, Bagcivan Ihsan, Cetin Meral
Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, 58140 Sivas, Turkey.
Eur J Pharmacol. 2006 Jan 20;530(3):263-9. doi: 10.1016/j.ejphar.2005.11.018. Epub 2006 Jan 4.
This study was designed to compare the effects of beta-adrenoceptor agonists formoterol and BRL 37344 on spontaneous contractions and the levels of cAMP and cGMP of myometrial strips isolated from timed-pregnant rats. Myometrial strips were obtained from term-pregnant Wistar albino rats (n=12), mounted in organ baths and tested for changes in isometric tension in response to formoterol and BRL 37344. We evaluated the effect of increasing concentrations of formoterol and BRL 37344 on oxytocin-induced myometrial contractions and on contractions of myometrial smooth muscle pretreated with metoprolol, ICI 118.551 and SR 59230A (beta1, beta2, beta3-adrenoceptor antagonist, respectively, 10(-6) M). Effects of formoterol and BRL 37344 on cAMP and cGMP levels in isolated myometrial strips (n=6) were evaluated by radioimmunoassay kits. Formoterol (10(-12)-10(-8) M) and BRL 37344 (10(-11)-10(-5) M) concentration-dependently decreased the amplitude of oxytocin-induced contractions. E(max) value (100%) of formoterol was increased significantly more than E(max) value (70.6%) of BRL 37344 (P<0.05), with no change in pD(2) value (9.54+/-0.12 and 9.12+/-0.12, respectively). The inhibition of the amplitude of oxytocin-induced contractions by formoterol was antagonized with ICI 118.551 (10(-6) M), but they were not changed by metoprolol (10(-6) M) or SR 59230A (10(-6) M). The inhibition of the amplitude of oxytocin-induced contractions by BRL 37344 were antagonized with SR 59230A (10(-6) M), but they were not changed by metoprolol (10(-6) M) or ICI 118.551 (10(-6) M). Formoterol and BRL 37344 increased cAMP levels. BRL 37344 increased cGMP levels in BRL 37344 group more than control group, but this increase is less significant than cAMP levels (P>0.05). Formoterol and BRL 37344 decreased amplitude of myometrial contractions with similar potency, but efficacy of formoterol was better than BRL 37344.
本研究旨在比较β-肾上腺素能受体激动剂福莫特罗和BRL 37344对从妊娠特定时期大鼠分离的子宫肌条自发收缩以及环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）水平的影响。子宫肌条取自足月妊娠的Wistar白化大鼠（n = 12），安装在器官浴槽中，检测福莫特罗和BRL 37344引起的等长张力变化。我们评估了福莫特罗和BRL 37344浓度增加对催产素诱导的子宫肌收缩以及用美托洛尔、ICI 118.551和SR 59230A（分别为β1、β2、β3-肾上腺素能受体拮抗剂，10⁻⁶ M）预处理的子宫肌平滑肌收缩的影响。通过放射免疫分析试剂盒评估福莫特罗和BRL 37344对分离的子宫肌条（n = 6）中cAMP和cGMP水平的影响。福莫特罗（10⁻¹² - 10⁻⁸ M）和BRL 37344（10⁻¹¹ - 10⁻⁵ M）浓度依赖性地降低催产素诱导的收缩幅度。福莫特罗的E(max)值（100%）比BRL 37344的E(max)值（70.6%）显著增加更多（P<0.05），pD(2)值无变化（分别为9.54±0.12和9.12±0.12）。福莫特罗对催产素诱导的收缩幅度的抑制作用被ICI 118.551（10⁻⁶ M）拮抗，但美托洛尔（10⁻⁶ M）或SR 59230A（10⁻⁶ M）对其无影响。BRL 37344对催产素诱导的收缩幅度的抑制作用被SR 59230A（10⁻⁶ M）拮抗，但美托洛尔（10⁻⁶ M）或ICI 118.551（10⁻⁶ M）对其无影响。福莫特罗和BRL 37344增加cAMP水平。BRL 37344组中BRL 37344使cGMP水平高于对照组，但这种增加不如cAMP水平显著（P>0.05）。福莫特罗和BRL 37344降低子宫肌收缩幅度的效力相似，但福莫特罗的效果优于BRL 37344。
