0231–424X/$ 20.00 © 2011 Akadémiai Kiadó, Budapest Acta Physiologica Hungarica, Volume 98 (3), pp. 329–338 (2011) DOI: 10.1556/APhysiol.98.2011.3.10 Complex effects of imatinib on spontaneous and oxytocin-induced contractions in human non-pregnant myometrium SM Cretoiu 1,2 * , AA Simionescu 3 * , L Caravia 1 , A Curici 1 , D Cretoiu 1,2 , LM Popescu 1,2 1 Department of Cellular and Molecular Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, 2 ‘V. Babeş’ National Institute of Pathology, Bucharest, and Obstetrics and Gynecology, Filantropia Hospital, Bucharest, Romania Received: April 5, 2011 Accepted after revision: April 23, 2011 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. Keywords: human myometrium, telocytes, c-kit, oxytocin, imatinib, interstitial cells Deciphering myometrial contractility continues to remain a major challenge for scientists focusing on molecular and cellular events that control uterine activity. The various approaches rely mainly on the two major sources of the Ca 2+ involved in the coupling of membrane depolarization to the cross-bridge cycling: entry across the sarcolemma through voltage-gated Ca 2+ channels and/or release from the sarcoplasmic reticulum (SR) (8, 30). Progress in understanding the myometrial contractile coordination has not been followed by similar advances in the clinical ability to manipulate uterine contractile dysfunctions. The regulation of uterine smooth-muscle contraction is under the control of circulating hormones, neurotransmitters and local factors. Among these hormones, oxytocin (OT) is an important agent for inducing labor (16, 37–39) and moreover the importance of OT influence on the non-pregnant myometrium increased significantly during the last years (26). Corresponding author: LM Popescu Department of Cellular and Molecular Medicine ‘Carol Davila’ University of Medicine and Pharmacy PO Box 35-29, Bucharest 35, Romania Fax: +40 21 312 4885; E-mail: LMP@jcmm.org * These authors have contributed equally.