Lovasz Norbert, Koncz Andrea, Domokos Dora, Gaspar Robert, Falkay György
György Falkay, Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, H-6701, P.O. Box 121, Hungary,
Croat Med J. 2015 Apr;56(2):114-8. doi: 10.3325/cmj.2015.56.114.
To investigate whether ATP-sensitive potassium (K(ATP)) channels modulate the tocolytic effect of β2-adrenergic receptor (β2-AR) agonists (ritodrine and salmeterol) in early-pregnant (day 6) and late-pregnant (day 22) rat uterus in vitro, in order to examine the relation between the K(ATP) channel sulphonylurea-binding regulatory subunit (SUR) expression and pharmacological reactivity of β2-AR agonists.
The tocolytic effects of ritodrine and salmeterol (10(-10)-10(-5) M) on spontaneous rhythmic contractions were investigated cumulatively, alone, or in the presence of the K(ATP) channel blocker glibenclamide (10(-6) M) and the K(ATP) channel opener pinacidil (10(-9)-10(-7) M) after 5-min preincubation.
β2-AR agonist induced myometrial relaxation was inhibited by glibenclamide and enhanced by pinacidil on day 6, when SUR1 expression levels were high. Neither glibenclamide nor pinacidil mediated tocolytic effect was measured on day 22.
Low expression of the K(ATP) channels at the end of gestation may facilitate enhanced excitability and contractility in the rat myometrium. The combination of a betamimetic and a K(ATP) channel opener will therefore not be of therapeutic relevance in the treatment of preterm delivery.
研究三磷酸腺苷敏感性钾（K(ATP)）通道是否调节β2 - 肾上腺素能受体（β2 - AR）激动剂（利托君和沙美特罗）对妊娠早期（第6天）和妊娠晚期（第22天）大鼠子宫的保胎作用，以探讨K(ATP)通道磺酰脲结合调节亚基（SUR）表达与β2 - AR激动剂药理反应性之间的关系。
累积研究利托君和沙美特罗（10⁻¹⁰ - 10⁻⁵ M）对自发性节律性收缩的保胎作用，单独使用或在预孵育5分钟后，于存在K(ATP)通道阻滞剂格列本脲（10⁻⁶ M）和K(ATP)通道开放剂吡那地尔（10⁻⁹ - 10⁻⁷ M）的情况下进行。
在第6天，当SUR1表达水平较高时，格列本脲抑制β2 - AR激动剂诱导的子宫肌层舒张，而吡那地尔增强该作用。在第22天未检测到格列本脲或吡那地尔介导的保胎作用。
妊娠末期K(ATP)通道的低表达可能促进大鼠子宫肌层兴奋性和收缩性增强。因此，拟β类药物与K(ATP)通道开放剂联合使用在早产治疗中可能无治疗意义。
