Abstract

In the gastrointestinal tract, interstitial cells of Cajal (ICCs) generate a pacemaker activity. They produce electric slow waves that trigger and coordinate gut smooth muscle contractions. Interstitial cells of Cajal's slender shape is revealed by KIT immunostaining. Based on several features, including KIT expression and KIT dependence, ICC-like cells were identified in nongastrointestinal tissues. Here, we investigated in the mouse whether uterine contractions depend on ICC-like cells' activity. By labeling KIT-expressing cells, we found putative ICC-like cells in the uterus, observed as KIT-positive interstitial, long spindle-shaped cells with fine branched cytoplasm processes, distributed in muscular layers and in subepithelial connective tissue. We then checked the potential KIT dependence of ex vivo contractile activity of the uterus by combining genetic and pharmacological approaches, using the Kit W-v hypomorphic mutation, and imatinib as a KIT noncompetitive inhibitor. We found a significant reduction in frequency of longitudinal uterine contractions in Kit W-v/Kit W-v compared with Kit+/+ mice, whereas amplitude was unaffected. There was no difference in frequency or amplitude of circular uterine contractions between Kit W-v/Kit W-v and Kit+/+ mice. Ex vivo treatment of Kit+/+ uterine horns with imatinib resulted in a dose-dependent reduction of the frequency and amplitude of longitudinal myometrial contractions. Amplitude and frequency of circular contractions were unaffected in presence of imatinib. These concurrent results suggest that longitudinal contractions of the uterus depend on a KIT signaling pathway of ICC-like cells. The existence of ICC-like cells in the myometrium may enhance our understanding of uterine spontaneous contractile activity and suggest new approaches for treatment of uterine contractility disorders.

Links

Publisher Full Text

Authors

Allix S, Reyes-Gomez E, Aubin-Houzelstein G, Noël D, Tiret L, Panthier JJ, Bernex F

Institution

Institut National de la Recherche Agronomique, UMR955 de Génétique Moléculaire et Cellulaire, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort, France.

Source

Biology of reproduction 79:3 2008 Sep pg 510-7

MeSH

Animals
Dose-Response Relationship, Drug
Duodenum
Electrophysiology
Female
Mast Cells
Mice
Mice, Transgenic
Myometrium
Piperazines
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-kit
Pyrimidines
Signal Transduction
Uterine Contraction
Uterus

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18480468