Original Article

The Effect of Imatinib Mesylate on the Contractility of Isolated Rabbit Myometrial Strips
G. Hutchings^a, J. Deprest^a, B. Nilius^b, T. Roskams^c, D. De Ridder^d

Departments of
^aObstetrics and Gynaecology,
^bPhysiology,
^cMorphology and Molecular Pathology, and
^dUrology, University Hospital Gasthuisberg, Leuven, Belgium

Address of Corresponding Author

Gynecol Obstet Invest 2006;62:79-83 (DOI: 10.1159/000092530)

  Key Words

• Imatinib mesylate
• Glivec
• Myometrium
• C-kit
• Interstitial cells

  Abstract

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 µM. 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 by imatinib mesylate affects only the amplitude of spontaneous contractions at concentrations, the equivalent of ×10-100 the normal therapeutic concentration.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

G. Hutchings
Centre for Surgical Technologies
Minderbroedersstraat 17
BE-3000 Leuven (Belgium)
Tel. +32 479 574039, Fax +32 1633 7821, E-Mail livvygraham@yahoo.co.uk

  Article Information

Received: November 11, 2005
Accepted after revision: February 23, 2006
Published online: April 3, 2006
Number of Print Pages : 5
Number of Figures : 2, Number of Tables : 2, Number of References : 18