Mental stress and gastric acid secretion

In 14 healthy male volunteers, we studied the influence of acute mental (=psychological) stress induced by performing mental arithmetic and solving anagrams against a financial reward on endogenously stimulated gastric acid output. Personality factors were determined by the Personality Research Form. Acute mental stress significantly (P<0.05) increased systolic blood pressure (+8.9±2.0 mm Hg±sem) and heart rate (+5.3±1.6 beatslmin). The mean gastric acid output during the mental stress period (17.9±2.7 mmol/32 min) did not significantly differ from pre- (16.9±2.3 mmol/32 min) and poststress (18.1±2.2 mmol/32 min) values. However, detailed analysis revealed that mental stress induced contrary changes of gastric acid output in different subjects. About half the individuals reacted with a decrease (up to 60%) and the other half with an increase (up to 60%) in acid output. In some individuals the changes of gastric acid output were very small. By multiple correlations, impulsivity was identified as the personality trait with the highest correlation coefficient (r=0.82) with changes of gastric acid output during the acute mental stress period. During the mental stress period, gastric acid output increased in subjects with high scores on the impulsivity scale, but significantly decreased in those with low scores. We conclude that (1) there is a great individual variability in gastric acid response to acute mental stress, and (2) this variability may be partly attributed to differences in personality traits.     

Intestinal fat digestion plays a significant role in fat-induced suppression of gastric acid secretion and gastrin release in the rat

We have investigated the role of intestinal fat digestion in fat-induced suppression of gastric acid secretion and gastrin release in the rat. Intraduodenal administration of oleic acid (10%, pH 6.5) and triglyceride (10%, pH 6.5) at a rate of 2 ml/hr resulted in significant suppression of gastric acid secretion and gastrin release stimulated by intragastric perfusion of peptone (0.5%). Diversion of pancreatic juice from the duodenum completely abolished triglyceride-induced inhibition of peptone-stimulated gastric acid secretion and plasma gastrin release, but oleic acid-suppressed gastric acid secretion and gastrin release were unaffected by pancreatic juice diversion. Intraduodenal administration of digested triglyceride, prepared by preincubation with lipase, caused significant suppression of the peptone-induced gastric acid secretion and rise in plasma gastrin levels, even though pancreatic juice was excluded. The results of this study indicate that digestive products of triglyceride by pancreatic juice, especially by lipase, are responsible for the intestinal fat-induced inhibition of gastric acid secretion and gastrin release and that intestinal fat digestion plays a significant role in the mechanism.Part of this work was presented at the Annual Meeting of the American Gastroenterological Association, May 19–22, 1991, New Orleans, and appeared in abstract form inGastroenterology 100:A160, 1991.     

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.     

Effects of gonadotropin-releasing hormone (GnRH) on gastric secretion and gastrin release in the dog

The effects of GnRH on gastric secretion and gastrin release from dogs provided with gastric fistulae and Heidenhain pouches have been investigated. A transient yet significant inhibition of pentagastrin-stimulated secretion from gastric fistulae was observed, while secretion from Heidenhain pouches was unchanged. The maximal inhibitory effect of GnRH on both acid and pepsin secretion stimulated by 2-deoxy-D-glucose was obtained from gastric fistulae. On the contrary, GnRH failed to affect either acid secretion stimulated by bethanechol or acid secretion and gastrin release induced by bombesin. The present results indicate that GnRH possesses an inhibitory action on gastric secretion from the vagally innervated stomach of the dog. The most likely inhibitory mechanism seems to be represented by a decrease of the vagal activity.     

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.     

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.     

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.     

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.     

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.     

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.     

GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon,inhibit gastric acid secretion in humans

Glucagon-like peptide 1 amide (GLP-1 amide), a predicted product of the glucagon gene (proglucagon 72-107-amide), and truncated GLP-1 (proglucagon 78-107-amide), recently isolated from porcine small intestine, were infused in doses of 100 and 400 ng/kg/hr and 12.5 and 50 ng/kg/hr, respectively, into eight volunteers to study pharmacokinetics and effects on pentagastrin- stimulated gastric acid secretion (plateau stimulation with pentagastrin at D ₅₀:100ng/kg/hr). The concentration of GLP-1 in plasma increased from 64±12 to 189±23 and 631±76 pmol/liter, respectively. The concentration of truncated GLP increased from approximately 7 pmol/liter to 28±3 pmol/liter during the high rate of infusion. A similar increase was seen in response to a mixed meal in eight normal volunteers. The metabolic clearance rate (MCR) of GLP-1 was 2.2±0.3 and 2.6±0.3 ml/kg/min, respectively, and the half- life in plasma was 17±2 min. The MCR of truncated GLP-1 was 13±2.8 ml/kg/min and the half- life 11.4±2.1 min. GLP-1 reduced the pentagastrin- stimulated acid secretion 16±9% during the low-rate infusion and 23±12% during the high rate (P<0.05). Truncated GLP-1 caused a 36±3% inhibition during the high infusion rate. Thus truncated GLP-1, a naturally occurring peptide, is a potent inhibitor of acid secretion in man and more so than GLP-1.This study was supported by the Danish Medical Research Council, Novo's Fond and Owesen's Fond.     

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.     

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.     

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.