Glivec Research Today is a free monthly online journal that collates and summarizes the latest research about Glivec, including details on gleevec, imatinib, cancer, treatment, side-effects.

Imatinib inhibits spontaneous rhythmic contractions of human uterus and intestine.

Popescu LM, Vidulescu C, Curici A, Caravia L, Simionescu AA, Ciontea SM, Simion S

Department of Cellular and Molecular Medicine, Carol Davila University of Medicine and Pharmacy, PO BOX 35-29, Bucharest 35, Romania. LMP@jcmm.org

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.

Published 11 September 2006 in Eur J Pharmacol, 546(1): 177-81.
Full-text of this article is available online (may require subscription).

© 2004-2008 Glivec Research Today. All Rights Reserved.