CCK elicits and modulates vagal afferent activity arising from gastric and duodenal sites

We have begun to identify and characterize the locations and response profiles of vagal afferent fibers sensitive to CCK in the rat upper gastrointestinal tract. We found gastric and duodenal vagal afferent fibers that respond to CCK and to intraluminal loads. CCK both sensitizes and amplifies the response to loads in these fibers but may do so through separate transduction mechanisms. Thus, meal-related signals arising from the presence of gastroduodenal loads and the release of endogenous CCK can be integrated at the level of the peripheral afferent vagus nerve. These findings are consistent with behavioral results, demonstrating that combinations of gastric loads and exogenous CCK are more effective in suppressing food intake than is either stimulus presented alone. Our findings that both gastric and duodenal vagal afferent fibers are sensitive to CCK suggest that meal-related CCK may act at a range of peripheral neural sites linking the upper gastrointestinal tract to the central nervous system substrates underlying the control of food intake. The mode of activation of gastric vagal afferent by endogenously released CCK may be an endocrine action of intestinally derived CCK. Alternatively, the novel finding of duodenal load-sensitive vagal afferents close to a site of CCK release provides a potential for local paracrine actions of endogenous CCK in the mediation of satiety.