CHOLECYSTOKININ IN THE REGULATION OF GASTRIC-ACID AND ENDOCRINE PANCREATIC-SECRETION IN HUMANS

In this study, a selective antagonist of cholecystokinin (CCK)-A recep tors, loxiglumide, was used to evaluate the role of CCK in the control of the release of gastrin and pancreatic hormones (insulin, glucagon, pancreatic polypeptide (PP), and somatostatin) after stimulation with exogenous CCK and ingestion of a standard liquid mixed meal in health y humans. Exogenous CCK-8, which induced a small but significant incre ase in gastric acid secretion, resulted in dose-dependent increments i n plasma PP levels without significant changes in plasma levels of ins ulin, glucagon, or somatostatin. Pretreatment with loxiglumide resulte d in a marked increase in CCK-induced gastric acid secretion and aboli shed the increments in plasma PP without alteration of plasma insulin, glucagon, or somatostatin levels. Ingestion of the liquid meal result ed in an immediate rise in intragastric pH from basal values of about 2 to pH 6 lasting 90-120 min, and this was accompanied by significant increments in plasma gastrin, insulin, glucagon, PP, and somatostatin. Administration of loxiglumide (1200 mg orally) caused a reduction in the postprandial intragastric pH and the two- to three-fold increase i n plasma gastrin. Plasma insulin and glucagon levels in tests with lox iglumide tended to increase, probably owing to accelerated gastric emp tying, whereas plasma PP and somatostatin were significantly reduced. This study provides evidence that CCK exerts an inhibitory effect on g astric acid secretion and plasma gastrin release as well as a stimulat ory influence on the release of PP and somatostatin via CCK-A receptor s but does not influence directly insulin or glucagon secretion in man .