Roles of substance P and ATP in the subepithelial fibroblasts of rat intestinal villi.

The ingestion of food and water induces chemical and mechanical signals that trigger peristaltic reflexes and also villous movement in the gut. In the intestinal villi, subepithelial fibroblasts under the epithelium form contractile cellular networks and closely contact to the varicosities of substance P and nonsubstance P afferent neurons. Subepithelial fibroblasts of the duodenal villi possess purinergic receptor P2Y1 and tachykinin receptor NK1. ATP and substance P induce increase in intracellular Ca(2+) and cell contraction in subepithelial fibroblasts. They are highly mechanosensitive and release ATP by mechanical stimuli. Released ATP spreads to form an ATP "cloud" with nearly 1μM concentration and activates the surroundings via P2Y1 and afferent neurons via P2X receptors. These findings suggest that villous subepithelial fibroblasts and afferent neurons interact via ATP and substance P. This mutual interaction may play important roles in the signal transduction of mechano reflex pathways including a coordinate villous movement and also in the maturation of the structure and function of the intestinal villi.