Effect of prolonged c-kit receptor inhibition by imatinib mesylate on the uterine contractility of pregnant rabbits.
BACKGROUND
The c-kit receptor expressed by interstitial cells in the gastrointestinal tract is crucial to their pacemaking function. The function of similar c-kit-expressing myometrial cells is unknown.


METHODS
Imatinib mesylate, a specific c-kit receptor antagonist, was administered to pregnant New Zealand white rabbits (term = 31 days, n = 35) from day 27 gestation by intramuscular injection twice daily at high (50 microg/kg) or medium (10 microg/kg) dose and compared with a control group injected with vehicle only. In a second phase, two further groups received imatinib at medium or low (1 mug/kg) dose for a longer duration starting from day 18 until delivery. Three does from the latter groups as well as controls underwent myometrial biopsy under general anesthesia after spontaneous vaginal birth. Contractility was recorded by isometric tensiometry. The outcome measures were delay of parturition and in vitro contractility characteristics.


RESULTS
High-dose imatinib induced early delivery when compared with the control group (28.6 vs. 30.7 days, p < 0.001). The other groups delivered at term. No effect on in vitro contractility was apparent in any of the groups.


CONCLUSIONS
c-kit receptor inhibition in pregnant rabbits does not delay significantly the length of gestation or change myometrial contractility in vitro.
Hutchings
G
G
Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Leuven, Belgium. graham.hutchings@student.kuleuven.be
Gevaert
T
T
Deprest
J
J
Nilius
B
B
De Ridder
D
D
D000818:Animals; D001549:Benzamides; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D006801:Humans; D000068877:Imatinib Mesylate; D007273:Injections, Intramuscular; D023421:Models, Animal; D009215:Myometrium / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D011743:Pyrimidines / Q000494:pharmacology*; D011817:Rabbits; D014590:Uterine Contraction / Q000187:drug effects*
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit