The effect of imatinib mesylate on the contractility of isolated rabbit myometrial strips

Background. C-kit receptor expressing interstitial cells generate and coordinate the electrical signals that control peristalsis in the gut. However, the function of interstitial cells in the myometrium is not known. Methods: (1) Sections of rabbit myometrium were subjected to immunohistochemical staining for the c-kit receptor. (2) Spontaneously contracting myometrial strips from New Zealand White rabbits near term were mounted in an organ bath and attached to a tension-recording device. The effect of increased concentrations of the c-kit receptor antagonist imatinib mesylate on these contractions was observed. The main outcome measures were the change in frequency, amplitude and duration of contraction. Results: (1) Multipolar cells expressing c-kit were identified in the fibromuscular septum confirming the presence of interstitial cells in rabbit myometrium. (2) Imatinib decreased the amplitude of contractions by approximately 20% at 100 mu M. No effect was seen at lower concentrations. No effect of imatinib on frequency or duration of contractions was observed at any of the concentrations studied. Conclusions: In isolated rabbit myometrium, acute inhibition of the c-kit receptor imatinib mesylate affects only the amplitude of spontaneous contractions at concentrations, the equivalent of x 10-100 the normal therapeutic concentration. Copyright (c) 2006 S. Karger AG, Basel.