Effect of endogenous and exogenous cholecystokinin on gastrin release in man and dog

Perfusion of the jejunum with physiological concentrations of a mixture of amino acids (MAA) strongly stimulates pancreatic secretion in man. Since cholecystokinin (CCK) resembles gastrin structurally, studies were undertaken to determine if jejunal MAA perfusion or exogenous CCK have an effect on gastrin release in man and to compare the results with those in the conscious dog. Normal human volunteers were studied following an overnight fast. A triple lumen tube was placed approximately 40 cm beyond the ligament of Treitz. The jejunum was perfused with either saline, MAA or MAA plus atropine (1 mg/l) at a rate of 11.4 ml/min. Other subjects received a CCK i.v. infusion (0.125 CHR U/kg/min). Three conscious mongrel dogs fitted with total fistulae, after an 18 hr fast, were given 0.125 CNR U/kg/min of either CCK or CCK octapeptide. Blood samples from man and dog were taken at fixed intervals and allowed to clot. Using a double antibody radioimmunoassay, serum gastrin levels were determined. CCK released endogenously by MAA perfusion in man was not found to affect circulating gastrin levels. When CCK was given i.v. in a 10% pure form, gastrin levels increased from 60 to 200 pg/ml. Atropine given by jejunal perfusion did not alter the exogenous CCK response. Cross reactivity between CCK and gastrin with the gastrin antibody could not be shown to be responsible for serum gastrin elevation. When CCK was given i.v. to dogs, gastrin levels were significantly increased (from 30 to 100 pg/ml), while CCK octapeptide did not have any effect on gastrin levels. Neither the physiological release of CCK in humans nor exogenous administration of CCK octapeptide in dogs at a dose equivalent to maximal stimulation of pancreatic secretion in humans altered significantly venous levels of gastrin. Therefore, the authors concluded that the rise in gastrin levels when CCK (10% pure) is given in man or dog exogenously is probably due to an impurity present in the CCK preparation.