The goal of this project is to determine the sensory and effector mechanisms mediating enterogastric reflex inhibition of gastric acid secretion by intestinal fat. Because cholecystokinin is emerging as a physiological regulator of acid secretion, its role in enterogastric acid inhibition specifically will be investigated. Indeed, this study is based on recent evidence indicating that CCK may stimulate a vago-vagal reflex inhibitory pathway from the intestine to the stomach. It is well known that the presence of nutrients in the intestine after a meal stimulates pancreatic protein and biliary secretion during the post- prandial period. In addition, dietary fats are an especially potent inhibitor of gastric emptying and acid secretion. There is good evidence that CCK is mediating at least the acid inhibitory response, but the transmission process and effector mechanism for the alteration of gastric acid secretion are not yet known. It is still not clear if CCK is acting principally as a hormonal inhibitor of acid secretion, or whether it can exert its effect on the stomach by neurally-mediated, paracrine release of gastric somatostatin. Therefore, this project will use in vivo regulatory physiology, electrophysiology, and immunohistochemistry to thoroughly investigate the enterogastric inhibitory pathways. Because CCK is a prime candidate to initiate this effect, these studies also will address the mechanisms of action of CCK as an enterogastrone.
