Background & Aims: The interstitial cell (IC) network may be of fundam
ental importance in regulating gastrointestinal motility. Intestinal s
mooth muscle cells are depolarized in the absence of ICs, and there ar
e no spontaneous slow waves. The messenger molecules between IC networ
k and smooth muscle are unknown. Exogenous administration of CO relaxe
s the opossum internal anal sphincter and the guinea pig ileum, and it
modulates potassium current and membrane potential of circular smooth
muscle cells of the human jejunum. The aim of this study was to deter
mine whether heme oxygenase (HO)-1 and HO-2, enzymes that catalyze the
production of CO, are present in the IC network of the mouse small in
testine. Methods: Antibodies specific for c-Kit, HO-1, and HO-2 were u
sed for immunohistochemistry. Confocal images were obtained and were v
olume rendered, and the images were converted into three-dimensional i
mages. Results: HO-2-like but not HO-l-like immunoreactivity was found
in IC networks associated with the myenteric plexus and the deep musc
ular plexus. Conclusions: HO-2 but not HO-1 is present in the IC cell
network of the mouse small intestine. The enzymatic activity of HO-2 w
ill result in the endogenous production of CO in IC networks of the mo
use small intestine.