Abstract
Subepithelial fibroblasts form a cellular network with gap junctions under the epithelium of gastrointestinal tract. The network keeps close contact with epithelium, capillaries and nerve terminals, and may play important roles in various signaling in intestinal villi. We found that they change cell-shape, depending on intracellular cAMP level and several bioactive substances such as endothelins (ETs), and that they release ATP by mechanical stress and transmit Ca2+ signal via P2Y activation in surrounding cells. These dynamical changes of their property may control mechanical and sieve properties of the network. Here, we have confirmed the sub-types of ET receptors using wild-phenotype and sl/sl rats, a deletion mutant of ETB gene, and also sub-types of ATP receptors. We have also clarified the cell-shape dependence of intercellular communication via mechanically released ATP and gap junctions. It is known that nerve terminals of mucosal sensory neurons distributes under the epithelium of villi and possess P2X receptors. The source of ATP was thought to be a release from enterochromaffin cells. However, the characteristics of subepithelial fibroblasts we made clear suggests that ATP is released from subepithelial fibroblasts by mechnical deformation of the villi. So, we propose that subepithelial fibroblasts work as a mechano-sensor in the intestine. A finding that neurons (NG108-15) co-cultured with subepithelial fibroblasts were activated by mechanically induced Ca2+-waves on subepithelial fibroblasts supports the idea. [Jpn J Physiol 54 Suppl:S76 (2004)]
