Studies of the effect of elevated levels of serum calcium on gastric secretion in dogs 1 7 indicate that there is no significant stimulation of acid secretion and that some degree of inhibition may occur.' In order to investigate the possible role of the gastrin mechanism in the stimulation of gastric secretion by infusion of calcium, we have studied the effects of the intravenous administration of calcium on gastric acid secretion and on the serum concentration of gastrin in duodenal ulcer patients and in normal individuals. We further tested the effect of calcium infusion on

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In man, oral or intravenous administration of ethanol caused a small but definite increase in peripheral serum gastrin concentration (measured by radioimmunoassay). In dogs, perfusion of the antrum with 10% ethanol caused an immediate increase in gastrin levels in the antral venous outflow. Acidification of the perfusate did not totally block the gastrin release from the antrum. Intravenous infusion of ethanol in dogs caused release of gastrin from the antrum.IN 1898, CHrTlENDEN AND cowoRERs3 reported that ingestion of ethanol stimulated gastric acid secretion. The mechanisms responsible for this stimulation are not entirely clear, but several studies suggest that at least two paths are involved: first, local contact of alcohol with antral mucosa seems to release gastrin",7",7"'8 and second, after its absorption, alcohol acts directly on the parietal cells.40o1618 The mechanism by which blood alcohol directly stimulates the oxyntic glands is not known.We have studied the characteristics of the release of gastrin (measured by radioimmunoassay) in response to local application of ethanol to the antral mucosa in man and in dogs. In addition, we have studied the effect of intravenous ethanol on basal serum gastrin levels in man and on gastrin release from the antrum in dogs. A double lumen catheter was inserted into the antrum via a stab wound in the duodenum for antral perfusion (250 ml/hr). The pylorus was ligated around the catheter, and the antral vein was cannulated as described previously."1 The antrum was perfused sequentially with physiologic saline (pH 5.0) for 30 minutes, 10% ethanol (pH 5.0) for 60 minutes, 10% ethanol (pH 1.0) for 60 minutes, and finally 10% ethanol (pH 7.0) for 30 minutes. Blood samples for serum gastrin determination were obtained in the basal state and at intervals throughout the experiment. Materials and Methods Effect of Intravenous Ethanol on Basal SerumGastrin Concentration Studies in Man. Six healthy volunteers were fasted overnight. After two basal blood samples were obtained for serum gastrin determination, 7% ethanol in 0.9% NaCl was infused into a peripheral vein at the rate of 4 ml/ kg/hr for 60 minutes. Blood samples were collected at intervals for 120 minutes after the infusion was started.Studies in Dogs. Six adult mongrel dogs were anesthetized, operated upon, and the stomachs were prepared as described in the studies on the local release of gastrin 906

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Acidification of the gastric antrum reduces the secretion from denervated and innervated fundic pouches in response to various stimuli (1-4). With sensitive radioimmunoassay technics it is possible to directly measure serum concentrations of gastrin released from the antrum during periods of variation in antral acidity (5). In the present work we report direct evidence on the timing of gastrin release after application of solutions at varying pH to antral mucosa which was not otherwise stimulated. Gastrin concentrations in blood draining the gastric antrum were measured by radioimmunoassay.Materials and Methods. Twelve adult mongrel dogs were divided into two groups of six. Each dog was fasted for 24 hr and anesthetized with pentobarbital sodium. At laparotomy the blood supply of the antrum was dissected to allow intermittent sampling of the antral venous outflow as described previously (6). The antrum was isolated from the fundus by means of a clamp placed across the antra-fundic junction. A doublelumen catheter for perfusion was placed via the duodenum into the antrum, and the pylorus was ligated around the catheter. During a 30 rnin basal period, the antral secretions were collected for determination of pH. Antral perfusion was then begun using solutions of 0.9% NaCl adjusted to pH vallues between 1.0 and 8.0. The rate of perfusion was 150 ml/hr; the inflow pressure was less than 2 cm H20 and visible distension of the pouch did not occur. Antral venous blood samples for gastrin measurement were obtained twice in the basal state (-15 min and zero time) and a t 15 min 1 Svpponted by grant AM 15241 from the National Institutes of Health and by a grant from The: John A. Hamtford Foundation, Inc. intervals throughout the experiments.I n six dogs (Group 1) continuous antral perfusion was begun a t pH 7.0, and every 30 min the pH of the perfusate was lowered by 1 unit in order to make the antrum more acid. In the other six dogs (Group 2) the antrum was perfiused for 30 min periods, first at pH 7.0, then serially a t pH 3.0, 8.0, 1.0 and 7.0. Sections of antral mucosa were taken for histologic study a t the end of each experiment. The gastrin concentrations in the serum of the antral venous blood were measured by radioimmunoassay ( 5 ) and are expressed as the mean of the observed values with the corresponding standard error (2 SE) . Student's t test was used to determine statistical significance of the data.Results. Irrigation of the antrum with solutions of varying acidity produced no histologic evidence of injury to antral mucosa.Group I (Fig. 1.) The results of measurement of gastrin values in antral venous blood in the six dogs are shown in Fig. 1. The mean basal serum gastrin was 172 t 23 pg/ml. The pH of the aspirated basal secretions from the antral pouch was between 3.5 and 5.0. Irrigation of the antrum with saline pH 7 increased the gastrin concentration to a peak of 390 t 69 pg/ml ( p < 0.02). Stepwise lowering of the pH of the antral perfusate resulted in progressive diminution in gastrin values. At pH 5 ...