Cretoiu S M, Simionescu A A, Caravia L, Curici A, Cretoiu D, Popescu L M
Department of Cellular and Molecular Medicine, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
Acta Physiol Hung. 2011 Sep;98(3):329-38. doi: 10.1556/APhysiol.98.2011.3.10.
Human myometrium includes two important cell populations involved in its contractility: smooth muscle fibers and interstitial cells. The pacemaking mechanism is not yet identified, but it is possible that myometrial smooth muscle cells contract in response to a signal generated by c-kit positive interstitial cells. The aim of this study was to investigate the effects of imatinib as a c-kit receptor antagonist on the spontaneous or oxytocin (OT) induced contractions of human non-pregnant myometrium in vitro. Myometrial strips were obtained from non-pregnant women (reproductive age) undergoing hysterectomy for benign indications. The strips were suspended in organ baths for recording of isometric tension. Imatinib effects were assessed on spontaneous contraction and after preexposure to OT.Direct exposure of myometrial strips to imatinib inhibits both amplitude and frequency of contractions (80-320 μM) in a dose dependent manner. Amplitude reverted back to 90% of the baseline amplitude by consequent addition of imatinib (until 480 μM). Total inhibition of myometrial contraction was obtained after addition of OT 60 nM. If myometrium was pre-exposed to OT (320 nM), imatinib 80-160 μm increased amplitude, while decreasing frequency. These data provide evidence that telocytes may be involved as modulators of the spontaneous contractions of the non-pregnant human uterus, via a tyrosine-kinase independent signaling pathway.
平滑肌纤维和间质细胞。起搏机制尚未明确，但子宫肌层平滑肌细胞有可能响应c-kit阳性间质细胞产生的信号而收缩。本研究的目的是调查伊马替尼作为一种c-kit受体拮抗剂对人非妊娠子宫肌层体外自发收缩或催产素（OT）诱导收缩的影响。子宫肌条取自因良性指征接受子宫切除术的非妊娠妇女（育龄期）。将肌条悬挂于器官浴槽中记录等长张力。评估伊马替尼对自发收缩以及预先暴露于OT后的影响。子宫肌条直接暴露于伊马替尼会以剂量依赖性方式抑制收缩的幅度和频率（80 - 320 μM）。随后添加伊马替尼（直至480 μM）时，幅度恢复至基线幅度的90%。添加60 nM OT后子宫肌层收缩完全被抑制。如果子宫肌层预先暴露于OT（320 nM），80 - 160 μm的伊马替尼会增加幅度，同时降低频率。这些数据提供了证据，表明间质细胞可能通过酪氨酸激酶非依赖性信号通路作为非妊娠人子宫自发收缩的调节因子参与其中。
