Cholecystokinin and nerotensin are two gastrointestinal peptides that appear to have important physiological roles in regulation of gastroinstestinal secretions and motility. Evaluation of the hormonal roles of these peptides is complicated by the existence of multiple molecular forms, each representing a fragment of a common precursor, for each peptide. Some of the forms that have been identified in tissue extracts and blood may be artifacts of isolation systems. The present studies will provide new information about the primary structure and principal secreted forms of cholecystokinin and neurotensin in dog and will determine the primary structure of cholecystokinin in man. The nature of fragments of the two hormones that occur naturally in blood and target organ extracellular fluid will be determined. The biological importance of these two peptides and their fragments as regulators of gastric function in dogs will be determined by measurement of all forms present during physiological stimulation and comparision of biological effects during endogenous stimulation of hormone release with effects obtained during exogenous administration of doses of each peptide found to exist naturally in order to reproduce the concentrations in blood and tissue found during endogenous stimulation. From these studies it should be possible to conclude whether or not the amounts of cholecystokinin or neurotensin peptides released by fat in the intestine are sufficient to explain physiological inhibition of acid secretion.
