Neither glycine-extended gastrin nor the 1-13 fragment of gastrin 17 influences gastric acid secretion in humans

The effect on gastric acid secretion of two gastrin 17-related peptides without the carboxyamide, i.e., the glycine-extended 5-17 fragment and the 1-13 fragment of human gastrin 17, was examined in normal subjects. Acid secretion was stimulated by an intravenous infusion of 21 pmol/kg.h of gastrin 17 or by intragastric instillation of peptone; gastric acid output during simultaneous infusion of 325 pmol/kg.h of the glycine-extended 5-17 fragment or 319 pmol/kg.h of the 1-13 fragment was then compared with acid output during infusion of saline. Neither the glycine-extended 5-17 fragment nor the 1-13 fragment of gastrin 17 influenced gastric acid secretion. By gel and ion-exchange chromatography of serum drawn during infusion, the infused peptide was recovered at the position of the intact synthetic peptide. The disappearance curve of circulating glycine-extended gastrin could be described by two components with half-lives of 3.6 and 48 min. As the glycine-extended fragment was stable in serum or plasma in vitro for 1 h at 37 degrees C, the rapid elimination observed in vivo cannot be ascribed to circulating plasma enzymes.     

Morphology of the gastric mucosa, gastric secretion and serum gastrin concentration following a test meal

In 32 subjects, the HCl secretion, the histological state of the antral and fundic mucosa and the gastrin response to a liquid meal extract were studied. Atrophy of the antrum was associated with normal gastrin concentration in the fasting state and after the test meal, in the presence of normal fundic mucosa and HCl secretion. In achlorhydria and atrophic gastritis, fasting gastrinemia was significantly elevated in subjects with a normal antrum, and only moderately increased in subjects with an atrophic antrum. The gastrin response to feeding was correlated to the fasting gastrin concentration in achlorhydric subjects with normal antral mucosa, in contrast to a uniformly reduced output in achlorhydric subjects with atrophic lesions of the antral mucosa.     

Action of beer and its ingredients on gastric acid secretion and release of gastrin in humans

The intragastric action of beer and its known ingredients before and after fermentation on gastric acid secretion and release of gastrin was studied in healthy humans. None of 11 tested ingredients of fermented beer (2 x 500 mL, pH 5.5, given either alone or in combination) or hop extract had any significant effect. Finished beer (6 weeks old) and new beer were potent stimuli of acid output, causing 93% and 76% of the incremental maximal acid output in response to pentagastrin (6 micrograms/kg SC), respectively. Before the addition of yeast, preproducts of beer were considerably less potent. Thus, first and finished wort caused only a minor acid response which was 48% and 46% of maximal acid output. Foreign fermentation in first and finished wort is presumably the reason for the stimulatory action because glucose solutions in concentrations (11.5% wt/vol) seen in wort did not stimulate acid secretion. However, glucose solutions to which yeast was added, resulting in fermentation, were as potent stimuli of acid secretion as beer. Lyophilization of beer at pH 11.0 and dialysis (cutoff mol wt, 1000) removed the stimulatory substances. The plasma gastrin responses paralleled the gastric acid response to the different stimulants. It was concluded that (a) the addition of yeast to finished wort and the following alcoholic fermentation are the essential steps for the stimulatory action of beer on gastric acid secretion and release of gastrin; (b) carbohydrate metabolites with a molecular weight of less than 1000 are the acid-stimulatory agents in fermented beer; and (c) gastrin is the mediator of the stimulation of acid secretion because all substances that had a potent acid-stimulatory action also were potent stimuli of gastrin release.     

Effect of optimum therapeutic dose of poldine on acid secretion, gastric acidity, gastric emptying, and serum gastrin concentration after a protein meal.

An oral optimum therapeutic dose of poldine was established in 5 normal subjects. Acid secretion in response to a protein meal was measured for 3 hr by continuous intragastric titration with sodium bicarbonate. Poldine 30 min before the meal reduced food-stimulated acid secretion from zero to 60% in the 5 subjects (average inhibition 32%). Poldine inhibited histamine-stimulated acid secretion to approximately the same extent. In separate experiments, gastric acidity after the meal was allowed to seek its natural level (i.e., there was notitration with bicarbonate). Poldine reduced average hydrogen concentration of the gastric contents by 85 to 50% from 1.5 to 3 hr after the meal. Since poldine did not alter the volume or the buffer content of the stomach, poldine inhibition of gastric acidity is due entirely to reduction of acid secretion and not to delayed emptying of food buffer. Poldine had no consistent effect on serum gastrin concentration after the meal when pH was maintained at a constant level by titration with bicarbonate; therefore, poldine inhibition of acid secretion is not mediated by a reduction of serum gastrin concentration.     

Action of ethanol and some alcoholic beverages on gastric acid secretion and release of gastrin in humans

The action of intragastric ethanol in various concentrations (1.4%-40% vol/vol) and of beer, white wine, cognac, and whisky on gastric acid secretion and release of gastrin was studied in healthy humans. Ethanol concentrations of 1.4% and 4% (vol/vol), but not higher, significantly (p less than 0.05) increased gastric acid secretion to 23% and 22%, respectively, of incremental maximal acid output [i.e., observed response to pentagastrin (6 micrograms/kg s.c.) minus basal acid output]. The 1-h incremental gastric acid responses to beer and wine were 96% and 61%, respectively, of incremental maximal acid output. Neither cognac nor whisky had any stimulatory effect. The 1-h incremental gastric acid response to an 8% peptone meal was 40% of incremental maximal acid output, and to peptone plus white wine 77%. Plasma gastrin levels were not altered by ethanol, cognac, and whisky. The 1-h integrated plasma gastrin responses to beer and white wine were 119% and 77%, respectively, of the response to the peptone meal. We conclude that (a) the action of pure ethanol on gastric acid secretion is related to its concentration: concentrations of 1.4% and 4% are moderate stimulants; concentrations of 5%-40% have no effect, or rather an inhibitory effect; (b) beer and white wine, but not whisky and cognac, are potent stimulants of gastric acid secretion; (c) the stimulatory mechanism of low ethanol concentrations is unknown; and (d) nonalcoholic constituents of beer and wine are most likely responsible for the stimulatory actions of both beverages on gastric acid secretion and release of gastrin.     

Effect of rioprostil, a synthetic prostaglandin E1 on meal-stimulated gastric acid secretion and plasma gastrin levels in humans

The effects of rioprostil (a newly developed synthetic prostaglandin E1 analogue) on meal-stimulated gastric acid secretion was evaluated in 8 healthy human volunteers. Gastric acid output was measured by intragastric titration on 4 different occasions. The following procedure was invariably employed: after a basal period of 45 min, 5 peptone meals (8%, 500 ml each) were given intragastrically in 45-min intervals and gastric acid output was measured continuously. 45 min after the first meal, either placebo or 150, 300 or 600 micrograms of rioprostil were given intragastrically in a randomized order and on different days. 15 min later, the second meal was given and intragastric titration continued. Rioprostil caused a dose-dependent inhibition of the 3-hour integrated gastric acid response to the peptone meals. The percentage of inhibition was 41, 68 and 79%, respectively, for 150, 300 and 600 micrograms of rioprostil. Whereas the inhibition by the two highest doses was statistically significant, this was not the case for the lowest dose of rioprostil. The integrated 3-hour plasma gastrin response to the peptone meals was not significantly changed by any of the doses of rioprostil. No significant adverse effects were observed with rioprostil.     

Fasting serum gastrin and basal gastric acid secretion.

The gastric secretion of acid was examined 30 minutes basally (BAO) and in response to stepwise increasing doses of pentagastrin in subjects with (n = 51) and without (n = 40) peptic ulcer disease. None of them showed basal anacidity. Before insertion of the gastric tube, blood was taken for radioimmunological determination of the serum gastrin concentration (SG). A significant positive correlation was found between SG and BAO in the subjects without ulcer. This was mainly due to a close correlation in 20 healthy young volunteers. When BAO and SG was expressed as proportions of calculated maximal acid response (Vmax) and half maximal dose of pentagastrin (Km), respectively, the positive correlation between SG and BAO was improved and reached significance also in the individuals with peptic ulcer disease. The findings suggest that the serum concentration of gastrin plays a role in the basal gastric secretion.     

Effect of terbutaline, a beta 2-adrenoreceptor agonist, on gastric acid secretion and serum gastrin concentrations in humans

Because beta-adrenoreceptor agonists inhibit gastrin-stimulated gastric acid secretion in animals, we postulated that the beta 2-adrenoreceptor agonist, terbutaline, would inhibit pentagastrin-stimulated acid secretion in humans. Moreover, we hypothesized that terbutaline might inhibit food-stimulated acid secretion, as gastrin is a major mediator of food-stimulated acid secretion. Subcutaneous terbutaline (0.25 mg) reduced acid secretion during intravenous infusion of a submaximal dose of pentagastrin by 30%-40% (p less than 0.005), even though terbutaline increased serum gastrin levels (p less than 0.05). Furthermore, subcutaneous (0.25 mg) or oral (5 mg) terbutaline, given before a homogenized steak meal was infused into the stomach, lowered mean food-stimulated acid secretion rates, despite enhanced postprandial serum gastrin concentrations. Terbutaline also increased serum gastrin concentrations in patients with Zollinger-Ellison syndrome and in vagotomized individuals. Thus, beta 2-adrenoreceptor agonists enhance gastrin release while at the same time inhibiting gastrin-stimulated acid secretion in humans.     

Effect of 1 week's administration of prednisone on gastric acid secretion and liberation of gastrin in healthy humans

In a double-blind, randomized study we examined the effects of an oral administration of prednisone (60 mg/day for 6 days) or placebo on gastric acid output basally (BAO), in response to peptone meals 1%, 2%, 4% and 8%, 500 ml each) and to pentagastrin 6 micrograms/kg s.c. to determine maximal acid output, MAO) and on plasma gastrin levels in 14 healthy volunteers. Gastric acid output was measured by intragastric titration (pH 5.5). For gastrin determination we used a specific radioimmunoassay. Experiments were performed one day (day 0) before giving the drugs and one day (day 7) and one month (day 30) after finishing the treatment. Both groups were comparable in their gastric acid responses on day 0. Six days treatment with prednisone did not significantly alter BAO, MAO and the gastric acid response to peptone and pentagastrin. Also, one month after finishing the treatment there were no significant differences in gastric acid output. Both groups had similar plasma gastrin levels on each day. Prednisone did not significantly alter plasma gastrin levels. We conclude that a six-day treatment with prednisone does not alter BAO, MAO and gastric secretory responses to peptone nor release of gastrin in healthy human volunteers.     

Alcohol and gastric acid secretion in humans.

The secretory response of gastric acid to pure ethanol and alcoholic beverages may be different because the action of the non-ethanolic contents of the beverage may overwhelm that of ethanol. Pure ethanol in low concentrations (< 5% vol/vol) is a mild stimulant of acid secretion whereas at higher concentrations it has either no effect or a mildly inhibitory one. Pure ethanol given by any route does not cause release of gastrin in humans. Alcoholic beverages with low ethanol content (beer and wine) are strong stimulants of gastric acid secretion and gastrin release, the effect of beer being equal to the maximal acid output. Beverages with a higher ethanol content (whisky, gin, cognac) do not stimulate gastric acid secretion or release of gastrin. The powerful stimulants of gastric acid secretion present in beer, which are yet to be identified, are thermostable and anionic polar substances. The effect of chronic alcohol abuse on gastric acid secretion is not as predictable. Chronic alcoholic patients may have normal, enhanced, or diminished acid secretory capacity; hypochlorhydria being associated histologically with atrophic gastritis. There are no studies on the acute effect of alcohol intake on gastric acid secretion in chronic alcoholic patients. The acid stimulatory component of beer and wine needs to be characterised and its possible role in the causation of alcohol induced gastrointestinal diseases needs to be investigated.     

Effect of proximal gastric vagotomy on gastric acid secretion and plasma gastrin

Sixteen patients underwent proximal gastric vagotomy (highly selective vagotomy) for chronic duodenal ulceration. All were subjected to preoperative and postoperative acid secretion studies. A reduction in the secretory response to pentagastrin and abolition of the response to meat extract occurred postoperatively.Plasma gastrin levels in response to meat extract were studied by radioimmunoassay. Basal plasma gastrin levels were unaffected by vagotomy and it was found that the plasma gastrin response to meat extract was not impaired after operation if the postoperative insulin test was positive. Only if the insulin test was negative was the amount of gastrin released by meat extract reduced.     

Effect of calcitonin on gastric emptying and on serum insulin and gastrin concentrations after ingestion of a mixed solid-liquid meal in humans

In a double-blind placebo-controlled study, we examined the effect of calcitonin on gastric emptying, and on serum concentrations of gastrin, insulin, glucose, calcium, and phosphorus after a mixed solid-liquid meal in 11 healthy men. Synthetic salmon calcitonin was administered as a 415 pmol i.v. bolus injection followed by a 90-min infusion to reach an overall dose of 62.25 pmol/kg body mass. Gastric emptying of a radiolabeled meal was surveyed by means of a gamma camera. A pronounced inhibition of gastric emptying with calcitonin was observed in all subjects (median gastric half emptying time 60.3 min after placebo versus 197.6 min after calcitonin; p less than 0.001). Calcitonin did not effect the postprandial gastrin release, nor did it change significantly the serum calcium or phosphorus concentrations. A decreased postprandial insulin release by calcitonin (mean +/- SEM area under the insulin curve 2,124.6 +/- 382.0 min mU L-1 after placebo versus 640.9 +/- 124.0 min mU L-1 after calcitonin; p less than 0.002) was accompanied by a different pattern of serum glucose concentrations during the infusion of the hormone when compared to the situation with a placebo. We discuss potential mechanisms and clinical relevance of our findings.     

Does sulfation of gastrin influence gastric acid secretion in man?

To assess the physiologic significance of tyrosine o-sulfation of gastrin in humans, the gastric acid stimulatory potencies of sulfated and non-sulfated human gastrin-17 were compared in six normal young subjects. Sulfated and non-sulfated forms of synthetic human gastrin-17 were infused intravenously in doses from 12.7 to 478 pmol/kg/h. Similar acid secretory responses were observed. The calculated maximal acid response for sulfated gastrin-17 was 35.7 +/- 4.3 mmol/h, and that for non-sulfated gastrin-17 was 39.8 +/- 7.5 mmol/h (mean +/- SEM, NS). The 50% effective dose of sulfated gastrin-17 was 22.2 +/- 6.7 pmol/kg/h, whereas it was 29.3 +/- 5.8 pmol/kg/h for non-sulfated gastrin-17 (NS). Finally, the 50% effective concentration of gastrin in serum was 34.7 +/- 5.0 pmol sulfated gastrin-17/l and 42.5 +/- 11.8 pmol non-sulfated gastrin-17/l (NS). The results show that tyrosine o-sulfation is without significant influence on the gastric acid secretory potency of gastrin in man. Moreover, the results also suggest that sulfated and non-sulfated gastrin-17 in man have similar rates of metabolism.     

Changes in gastric acid secretion assayed by endoscopic gastrin test before and after Helicobacter pylori eradication

BACKGROUND: It remains controversial whether or not Helicobacter pylori infection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed. AIM: To investigate by EGT the effects of H pylori eradication on the state of gastric acid secretion in patients with peptic ulcer. METHODS: Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whom H pylori infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after H pylori eradication. RESULTS: In patients with duodenal ulcer, the mean EGT value before H pylori eradication was higher than that in H pylori negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer before H pylori eradication was lower than that in H pylori negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value. CONCLUSIONS: The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of H pylori.     

Influence of verapamil on gastric acid secretion and gastrin release in dogs

Gastric secretion is supposed to be calcium-dependent. The effect of verapamil (0.3 mg/kg/h i.v.), a calcium channel-blocking agent, on stimulated gastric acid secretion and gastrin release was investigated in 8 mongrel dogs. Stimulation was either performed by bombesin (1.0 microgram/kg/h i.v.) or by insulin (0.3 U/kg i.v.). Verapamil significantly inhibited both the bombesin- and the insulin-stimulated gastric acid secretion. Mean total gastric acid output over a 120-min period was 9.5 +/- (SEM) 2.2 mmol after bombesin stimulation and 6.3 +/- 2.0 mmol after bombesin and verapamil (p less than 0.01). The respective values were 15.3 +/- 2.0 mmol for insulin stimulation and 7.0 +/- 1.6 mmol for insulin and verapamil (p less than 0.01). There was no significant influence of verapamil on plasma gastrin concentrations. Thus, the impairment of acid secretion by verapamil is not due to an inhibition of gastrin release in intact dogs.