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.     

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.     

Effect of nifedipine on gastric acid secretion and gastrin release in man

The role of nifedipine in inducing the blockage of calcium slow channels in the smooth muscle cell of the esophagus is well known. The aim of our study was to evaluate the action nifedipine exerts upon acid secretion and gastrin release stimulated by intragastric titration with a peptone meal (pH 5.5) in 7 healthy adult males. Percentage gastrin variations were constantly lower after oral administration of 20 mg nifedipine than with placebo. However, IGO values were shown to be not significantly different (9.3 +/- 1.8 vs 8.4 +/- 2.1 ng. min/ml). No variations in acid output were observed throughout the entire examination period (120 min). In our experience, therefore, nifedipine - under experimental conditions - proved unable to interfere with gastric secretion, probably due to the absence of specific receptors on the parietal and antral cell.     

Dose-response study of omeprazole on meal-stimulated gastric acid secretion and gastrin release

In a placebo-controlled, double-blind, crossover, and randomized trial, the effect of 30, 60, and 90 mg of oral omeprazole on peptone-stimulated gastric acid secretion and synchronously measured gastrin release was studied in 8 healthy subjects. Peptone-stimulated acid output was reduced dose-dependently by 42%, 80%, and 92%, respectively. In spite of a short mean plasma half-life of 52 min, the inhibitory effect lasted for greater than 4.5 h and was significantly correlated to the area under the plasma concentration time curve for omeprazole. Mean basal serum gastrin and gastrin profiles increased insignificantly without alteration of integrated gastrin output and did not show any correlation either to the omeprazole area under the plasma concentration time curve or to the inhibition of peptone-stimulated acid secretion. Side effects, significant alterations of laboratory screen, or alterations of serum concentrations of thyroid hormones were not detected. In conclusion, omeprazole is a potent and, under the conditions tested, well-tolerated inhibitor of meal-stimulated gastric acid secretion in humans.     

Effects of nifedipine on gastric acid secretion and gastrin release in man.

As calcium is important in the regulation of gastric acid secretion and gastrin release, we have examined the effect of the calcium antagonist nifedipine on these processes in man. Nifedipine 30 mg orally inhibited basal acid output by 37% (p less than 0.025) and that stimulated by low infusion rates of pentagastrin--that is, 0.031 and 0.062 microgram/kg/h by 44% (p = 0.05) and 39% (p less than 0.02) respectively. On increasing the pentagastrin infusion rate the inhibition was surmounted suggesting it was competitive in type. Nifedipine did not affect basal or Oxo meal stimulated gastrin concentrations in normal volunteers nor did it affect resting serum gastrin or calcium stimulated increase in gastrin in a single patient with Zollinger-Ellison syndrome. These findings are consistent with the transmembrane flux of calcium ions being involved in basal and pentagastrin stimulated acid secretion in man.     

Gastric acid secretion and gastrin and gastric inhibitory polypeptide release in cirrhotic patients

Gastric acid secretion, incidence of gastric mucosal lesion, and gut hormone responses were studied in 24 patients with liver cirrhosis. Gastric acid output in these subjects showed normal acidity and was nearly similar to that in patients with gastric ulcer. The incidence of gastric mucosal lesion was high, especially in patients whose plasma disappearance rate of indocyanine green was low. Plasma levels of both gastric and gastric inhibitory polypeptide were higher in cirrhotic patients than in control subjects both in the fasting state and after the ingestion of a test meal. Gel chromatography of the postprandial plasma of cirrhotics showed a higher immunoreactivity at the second peak than in controls. This is because cirrhotics have a higher percentage of authentic gastric inhibitory polypeptide, although the elution patterns were similar in both groups. It is suggested that impairment of extraction of some molecular components of both gastric and gastric inhibitory polypeptide may occur in the cirrhotic liver.     

Variable contribution of gastrin to gastric acid secretion after a meal in humans

The purpose of these experiments was to determine the contribution of gastrin to the acid secretory response to eating in healthy human subjects. To simulate the gastric and intestinal phases of eating, a meal was homogenized and then infused into the stomach through a nasogastric tube. At the same time, the cephalic phase of acid secretion was activated by sham feeding. With this simulated meal, mean serum gastrin concentration increased from a basal value of 43 +/- 9 pg/ml to an average postprandial gastrin concentration over 2 h of 121 +/- 25 pg/ml. Gastrin release after this simulated meal was similar to gastrin release after a normally eaten meal in the same 12 subjects. Gastric acid secretion in response to the simulated meal, which was measured by in vivo intragastric titration, averaged 24.2 +/- 2.4 mmol/h. To determine how much of this postprandial acid secretion could be attributed to gastrin, gastrin 17 I was infused intravenously in the same subjects on a separate day and acid secretion and serum gastrin concentrations were measured. By relating serum gastrin concentration during gastrin 17 infusion to concomitant acid secretion, we determined that an average postprandial serum gastrin concentration of 121 pg/ml could result in an acid secretion rate of 21.5 mmol/h, 89% of the actual acid secreted after the simulated meal in these subjects. However, in individual subjects, the amount of gastrin released after a meal could produce as little as 51% or as much as 162% of actual postprandial acid secretion. Thus, in individual human subjects the contribution of gastrin to acid secretion after a meal is variable.     

Effect of gastrin receptor antagonists on gastric acid secretion and gastrin and somatostatin release in the rat stomach.

The effects of two recently developed gastrin receptor antagonists, PD 136450 and L-365,260, on pentagastrin-stimulated acid secretion were investigated in rats. PD 136450 at a dose of 6 mg/kg s.c. (9.6 mumol) completely abolished acid secretion induced by pentagastrin. The inhibition of 18 mg/kg PD 136450 s.c. lasted for at least 8 h and was still effective after 14 days of treatment (18 mg/kg s.c. every 8 h). Acute application of L-365,260 at a dose of 3.8 mg/kg, which is equimolar (9.6 mumol) to 6 mg/kg PD 136450 reduced acid responses slightly. However, when L-365,260 was administered intravenously at a dose of 3 mg/kg, this antagonist completely abolished the pentagastrin-stimulated acid secretion. Furthermore, the effect of PD 136450 on endogenous gastric somatostatin and gastrin releases was tested in the isolated, vascularly perfused rat stomach. PD 136450 perfused at a concentration of 1 microM slightly increased somatostatin secretion after stimulation with a high dose of isoproterenol (10(-7) M). There was no effect of PD 136450 on basal or acetylcholine-stimulated gastrin secretion.     

Intracolonic fat inhibits gastric acid secretion independent of gastrin release in the dog

The purpose of this study was to examine the effect of perfusion of the colon with a fatty acid (oleic acid) on peptone-stimulated gastric acid secretion and release of gastrin in conscious dogs. Gastric acid secretion was monitored by continuous intragastric titration. Perfusion of the colon with sodium oleate (24 mmol/hr) inhibited gastric acid secretion (14.2±2.6 meq/hr) stimulated by a peptone meal (1%) significantly (P<0.05) when compared to perfusion of the colon with saline alone (20.1±1.6 meq/hr). The serum elevation, in gastrin in response to intragastric instillation of the peptone meal was not affected by the colonic perfusion of oleic acid. Plasma concentrations of peptide YY (PYY) increased significantly in response to perfusion of the colon with saline or sodium oleate, and the integrated release of PYY in response to sodium oleate 16.9±2.8 ng (60–120) min/ml] was significantly greater than the response to saline [3.1±0.7 ng (60–120) min/ml]. The results of this study indicate that inhibition of gastric acid secretion by perfusion of the colon with fat is not due to an inhibition of gastrin release. In addition, because PYY is an inhibitor of gastric acid secretion, it is possible that PYY participates as an inhibitor of gastric acid secretion by the colon.Supported by grants from the National Institutes of Health (5R37 DK 15241, P01 DK 35608) and a NATO collaborative research grant (0014/89).     

Paradoxical effects of gastrin releasing peptide on gastrin release and gastric secretion in the rat

The effects of gastrin releasing peptide (GRP) on gastrin release and gastric secretion were studied in anesthetized rats. Intravenous infusion of GRP (1-16 micrograms/kg/hr) caused a dose-dependent increase in serum gastrin level, however, it had no effect on basal gastric secretion in the lumen-perfused stomach preparation. Furthermore, GRP inhibited gastric secretion stimulated by pentagastrin or histamine dose-dependently, but not by carbachol. Simultaneous infusion of GRP and a beta adrenergic blocking agent, propranolol, an inhibitor of somatostatin release, did not alter the inhibitory effect of GRP on pentagastrin-stimulated gastric secretion. These results suggest that the inhibitory effect of GRP on gastric secretion in a stimulated condition is mediated via peptide hormones coreleased by GRP, and not via beta-adrenergic pathways.     

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.     

Effect of peptide YY on gastric acid secretion, gastrin and somatostatin release in the rat

The influence of PYY on stimulated gastric acid secretion and the possible role of gastric somatostatin was measured in rats. PYY, infused intravenously at a dose of 800 pmol/kg/h, reduced pentagastrin (20.8 nmol/kg/h) stimulated gastric acid secretion by 34 +/- 3%, whereas in controls acid secretion remained constant throughout the 90 min observation period. In a second series the effect of PYY on the endogenous gastric somatostatin-like immunoreactivity and gastrin-release was tested in the isolated, vascularly perfused rat stomach. PYY perfused at concentrations of 10 pM to 100 nM did not change either somatostatin or gastrin secretion from the rat stomach in vitro. The study shows that PYY suppressed acid secretion in the rat. Endogenous somatostatin or gastrin is unlikely to mediate the inhibitory effect of PYY on acid production.     

Gastric acid secretion and gastrin release in the baboon

Significant species differences have been demonstrated in gastric physiology, a factor that limits extrapolation of animal data to man. Primate physiology is thought to be similar to that of man; however, gastric function has not been adequately documented in the primate. In the present study six baboons (body weight 25.5±1.8 kg) were trained to sit in a chair and gastric acid secretion and gastrin release was studied in conscious animals. Mean basal acid secretion was 1.3±0.1 mmol (H⁺)/hr. Maximum output after pentagastrin (12 g/kg/hr) was 9.5±0.9 mmol (H⁺)/hr and 11.0±0.4 mmol (H⁺)/hr after histamine (40 g/kg/hr). A statistically significant (by cosinor analysis) circadian rhythm was demonstrated for intragastric pH over 24 hr in fasted baboons (P<0.001). Mean basal serum gastrin level was 37.7±8.3 pg/ml. The integrated gastrin response after administration of a protein rich meal was 2.52±0.07 ng×min/ml and this increased to 5.17±0.18 ng×min/ml (P<0.05) following simultaneous administration of a meal with atropine (0.2 mg/kg) (P<0.05). Our results suggest that there is significant basal and stimulated acid secretion in the baboon; the amount of acid secreted is similar to that reported in man. Gastric pH demonstrated a circadian rhythm. Postprandial gastrin release was significantly enhanced by cotreatment with atropine. As the present findings are similar to those previously reported in man, the baboon may be a useful model for further studies in gastric physiology and experimental peptic ulceration.     

Effects of somatostatin on gastric secretion and gastrin release in man.

Somatostatin, a recently synthesized hypothalamic growth hormone release-inhibiting factor (GIF), was used in the cyclic and linear form. In all subjects studied, the cyclic GIF inhibited gastrin secretion during basal conditions as well as during a standard food stimulus, with immediate rebound after the infusion was stopped. Similar responses were observed in a hypophysectomized patient, indicating that this effect of GIF was independent of suppression of growth hormone secretion. Cyclic and linear GIF, when administered in normal subjects during an infusion of synthetic human gastrin I, almost totally suppressed gastric secretion. The results indicate that GIF is a potent inhibitor of gastric secretion and gastrin release.     

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.     

Soy protein meals stimulate less gastric acid secretion and gastrin release than beef meals

Soy protein is a widely used, inexpensive, and nutritious source of dietary protein. In contrast to beef protein, the effects of soy protein on gastric acid secretion and serum gastrin concentration have not been evaluated. We compared the effects of meals containing the same amounts of either isolated soy or beef protein on acid secretion and serum gastrin concentration in normal humans. Acid secretion measured by in vivo intragastric titration was 30%-40% less with soy than beef protein (p less than 0.05), whether isolated soy protein alone was compared with a mixed beef meal containing carbohydrate and fat or whether soy or beef meals containing similar amounts of fat were compared. Average gastrin rises were 65%-75% less with soy than with beef (p less than 0.01). The explanation for less gastrin release with soy than with beef is unclear, but lower serum gastrin concentrations with soy probably accounted for reduced acid secretion. These results indicate that the source of dietary protein in a meal may be an important determinant of gastric acid secretion and gastrointestinal hormone release.     

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.