Popescu Laurentzio M, Vidulescu Cristina, Curici Antoanela, Caravia Laura, Simionescu Anca A, Ciontea Sanda M, Simion Sorin
Department of Cellular and Molecular Medicine, Carol Davila University of Medicine and Pharmacy, PO BOX 35-29, Bucharest 35, Romania.
Eur J Pharmacol. 2006 Sep 28;546(1-3):177-81. doi: 10.1016/j.ejphar.2006.06.068. Epub 2006 Jul 5.
The interstitial cells of Cajal (ICC) in the digestive tract and ICC-like cells in extradigestive organs express the c-kit tyrosine-kinase receptor, and have been implicated as pacemakers of smooth muscle spontaneous activity. We used imatinib mesylate (Glivec) to investigate whether c-kit activity of Cajal-like cells in human myometrium is involved in spontaneous rhythmic contractions of human uterine smooth muscle, taking intestinal smooth muscle as a reference tissue. We show that imatinib concentration-dependently inhibited the myogenic contractions of human myometrium in the organ bath, while it significantly affected noradrenaline or K(+)-induced contractions only at concentrations exceeding 50 muM. An inhibitory antibody directed against the extracellular domain of the platelet derived growth factor receptor (PDGFR), another target of imatinib that is expressed by the uterine muscle cells themselves, failed to affect myogenic contractions. These results suggest that Cajal-type cells of human myometrium, as well as ICC of intestinal smooth muscle, participate in myogenic contractile mechanisms, via a novel ligand-independent c-kit/CD117 tyrosine-kinase signaling.
消化道中的 Cajal 间质细胞（ICC）以及消化外器官中的 ICC 样细胞表达 c-kit 酪氨酸激酶受体，并被认为是平滑肌自发活动的起搏细胞。我们使用甲磺酸伊马替尼（格列卫），以肠道平滑肌作为参照组织，研究人子宫肌层中 Cajal 样细胞的 c-kit 活性是否参与人子宫平滑肌的自发节律性收缩。我们发现，在器官浴槽中，伊马替尼浓度依赖性地抑制人子宫肌层的肌源性收缩，而仅在浓度超过 50μM 时，它才会显著影响去甲肾上腺素或 K⁺诱导的收缩。一种针对血小板衍生生长因子受体（PDGFR）细胞外结构域的抑制性抗体，该受体是伊马替尼的另一个靶点且由子宫肌细胞自身表达，却未能影响肌源性收缩。这些结果表明，人子宫肌层的 Cajal 型细胞以及肠道平滑肌的 ICC，通过一种新的非配体依赖性 c-kit/CD117 酪氨酸激酶信号传导，参与肌源性收缩机制。
