Chanrachakul Boonsri, Broughton Pipkin Fiona, Khan Raheela N
Center for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, Academic Division of Obstetrics and Gynaecology, The Medical School, Derby City General Hospital, Uttoxeter New Road, Derby DE22 3DT, UK.
Am J Physiol Cell Physiol. 2004 Dec;287(6):C1747-52. doi: 10.1152/ajpcell.00236.2004. Epub 2004 Aug 25.
The beta(2)-adrenergic receptor (beta(2)-AR) and the large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel have been shown, separately, to be involved in mediating uterine relaxation. Our recent studies reveal that the levels of both beta(2)-AR and BK(Ca) channel proteins in pregnant human myometrium decrease by approximately 50% after the onset of labor. We present direct evidence in support of a structural and functional association between the beta(2)-AR and the BK(Ca) channel in pregnant human myometrium. Localization of both proteins is predominantly plasmalemmal, with 60% of beta(2)-AR colocalizing with the BK(Ca) channel. Coimmunoprecipitation studies indicate that BK(Ca) and beta(2)-AR are structurally linked by direct protein-protein interactions. Functional correlation was confirmed by experiments of human myometrial contractility in which the BK(Ca) channel blocker, paxilline, significantly antagonized the relaxant effect of the beta(2)-AR agonist ritodrine. These novel findings provide an insight into the coupling between the beta(2)-AR and BK(Ca) channel and may have utility in the application of this signaling cascade for therapeutic potential in the management of preterm labor.
β2-肾上腺素能受体（β2-AR）和大电导钙激活钾通道（BKCa）已分别被证明参与介导子宫舒张。我们最近的研究表明，在分娩开始后，妊娠子宫肌层中β2-AR和BKCa通道蛋白的水平均下降约50%。我们提供了直接证据，支持妊娠子宫肌层中β2-AR与BKCa通道之间存在结构和功能关联。两种蛋白的定位主要在质膜，60%的β2-AR与BKCa通道共定位。免疫共沉淀研究表明，BKCa和β2-AR通过直接的蛋白质-蛋白质相互作用在结构上相连。通过人子宫肌层收缩性实验证实了功能相关性，其中BKCa通道阻滞剂帕吉林显著拮抗β2-AR激动剂利托君的舒张作用。这些新发现为β2-AR与BKCa通道之间的偶联提供了见解，并且可能在将这种信号级联应用于早产管理的治疗潜力方面具有实用性。
