Zafrah Hind A, Alotaibi Mohammed F
Department of Physiology, College of Medicine, King Khalid University, Abha, Kingdom of.
Department of Physiology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Kingdom of.
J Basic Clin Physiol Pharmacol. 2017 May 1;28(3):209-217. doi: 10.1515/jbcpp-2016-0118.
The mechanisms underlying the onset of labor are not fully understood. Extracellular adenosine 5'-triphosphate (ATP) is known to cause uterine contractions in different species but the exact underlying mechanisms are poorly investigated to date. The aims of this study were to investigate the effect of extracellular ATP on spontaneous uterine contractions from different gestational stages and to elucidate its possible underlying mechanisms.
Longitudinal uterine strips were obtained from rats in different gestational stages (nonpregnant, late-pregnant, and term-pregnant). The effects of 1 mM ATP were examined on uterine contractions generated spontaneously, depolarized by high-KCl (60 mM), induced by oxytocin (5 nM), in the presence of high external Ca2+, or in the absence of external Ca2+.
Application of 1 mM extracellular ATP significantly increased the force of spontaneous contraction in uterine strips obtained from all gestational stages with prominent increase in term-pregnant rats compared to other gestations. ATP significantly increased the force induced by depolarization (122%, p=0.010, n=6), oxytocin (129%, p=0.001, n=7), high-Ca2+ (145%, p=0.005, n=6) and it was able to cause transient contraction in the absence of external Ca2+ (33%, p<0.01).
Extracellular ATP is able to increase the force and frequency of uterine contractions and its effect increases with the progression of pregnancy and it involves Ca2+ influx and release. These findings open a new window for clinicians to consider ATP as a therapeutic target to control the uterine activity during difficult labors.
分娩发动的潜在机制尚未完全明确。已知细胞外5'-三磷酸腺苷（ATP）可引起不同物种的子宫收缩，但迄今为止，其确切的潜在机制研究较少。本研究旨在探讨细胞外ATP对不同妊娠阶段子宫自发收缩的影响，并阐明其可能的潜在机制。
从处于不同妊娠阶段（未孕、妊娠晚期和足月妊娠）的大鼠获取子宫纵条。检测1 mM ATP对自发产生的子宫收缩、高钾（60 mM）去极化诱导的子宫收缩、催产素（5 nM）诱导的子宫收缩、高细胞外钙存在时或无细胞外钙时子宫收缩的影响。
应用1 mM细胞外ATP可显著增加所有妊娠阶段子宫条的自发收缩力，与其他妊娠阶段相比，足月妊娠大鼠的增加更为显著。ATP显著增加去极化（122%，p = 0.010，n = 6）、催产素（129%，p = 0.001，n = 7）、高钙（145%，p = 0.005，n = 6）诱导的收缩力，并且在无细胞外钙时能够引起短暂收缩（33%，p < 0.01）。
细胞外ATP能够增加子宫收缩的力度和频率，其作用随妊娠进展而增强，且涉及钙内流和释放。这些发现为临床医生将ATP作为控制难产时子宫活动的治疗靶点打开了一扇新窗口。
