Gastric Acid Secretion In Response Research Articles

Gastric morphological and functional changes produced by bile in the canine stomach.

Bile diverted into the canine stomach produced histological changes in gastric mucosa of mucus depletion, focal loss of epithelial cell height and focal epithelial degeneration that were maximal around the stoma. Bile depressed the gastric acid secretory response to both pentagastrin and histamine, but produced no change in fasting serum gastrin levels. The preparation used (cholecystogastrostomy) caused an elevation of both alkaline phosphatase and serum glutamic pyruvic transaminase.

Effect of bombesin-stimulated gastrin on gastric acid secretion in man

The effect of bombesin on gastrin release and gastric acid secretion was investigated in 10 healthy volunteers. Bombesin (0.6 μg · Kg −1 · hr −1) produced a significantly higher ( p < 0.001) increase in plasma gastrin levels (86.7 11.1 pmo/1 than after a protein meal (39.6 ± 5.6 pmol1/1). The gastric acid secretory response to bombesin (12.1 ± 2.9 mEq · hr −1) was however significantly lower ( p < 0.005) than the maximal response produced by pentagostrin (20.9 ± 3.5 mEq · hr −1) at the dose of 6 μg · Kg −1. Atropine did not modify gastrin release induced by bombesin but significantly reduced gastric acid secretion ( p < 0.01) . From the data presented it may be hypothesized that less biologically active forms of gastrin and/or other peptides inhibiting the gastrin effect upon gastric acid secretion may be released by bombesin.

Effect of naloxone and morphine on gastric acid secretion and on serum gastrin and pancreatic polypeptide concentrations in humans

To evaluate the role of endogenous opiates on gastric acid secretion, we infused naloxone, a pure opiate antagonist drug, into 8 healthy subjects in the basal state and then after an amino acid meal. Naloxone significantly reduced basal acid secretion and the gastric acid secretory response to the meal. Maximal inhibition averaged 65% for basal acid secretion and 35% for meal-stimulated secretion. Naloxone had no effect on serum gastrin concentrations or on the rate of gastric emptying of the meal. In the same subjects morphine also significantly reduced meal-stimulated acid secretion. In contrast to naloxone, morphine delayed gastric emptying and also enhanced the gastrin response to the meal. Morphine also abolished the pancreatic polypeptide response to the meal. Our studies with naloxone suggest that endogenous opiates may augment gastric acid secretion in humans. Failure of exogenous opiates to increase acid secretion suggests that actions other than opiate receptor stimulation (such as anticholinergic effects) may have come into play during morphine infusion.

Effect of Sham Feeding on Gastric Emptying

We studied the effect of vagal stimulation by sham feeding on gastric emptying in normal human subjects. When a saline test meal was infused into the stomach, simultaneous sham feeding did not alter the emptying of a nonabsorbable marker added to the meal or the volume of fluid emptied from the stomach. When a homogenized steak meal was infused, sham feeding caused a slight acceleration of emptying (47 +/- 2 vs. 53 +/- 2% marker recovered from the stomach 45 min after the meal, P less than 0.05). Gastric acid secretion in response to both meals was significantly augmented by sham feeding. Our results suggest that vagal stimulation by sham feeding has no effect on the emptying of isotonic saline and only a monor effect on gastric emptying of homogenized food in humans.

Serum Gastrin During Intestinal Phase of Acid Secretion in Dogs

These studies were designed to determine whether the intestinal phase of gastric acid secretion is accompanied by an increase in serum gastrin concentration. Seven dogs with a gastric fistula and a duodenal fistula prepared so as to allow perfusion into the duodenum without reflux into the stomach were used. Gastric secretion and blood samples for serum gastrin determination were collected during intestinal perfusion with either 0.15 M NaCl or 5% liver extract at 200 ml hr(-1) for 2 hr. The mean +/- SE gastric acid secretory response during the second hour of perfusion with 0.15 M NaCl was 3.1 +/- 1.0% of the maximal acid output (MAO) to histamine, significantly (P less than 0.05) greater than the control value with no intestinal perfusion (0.18 +/- 0.07%). The mean +/- SE response during the second hour of perfusion with 5% liver extract was 7.4 +/- 2.2% of MAO, significantly (P less than 0.05) greater than both control and NaCl perfusion values. There was no significant change in peripheral serum gastrin concentration during the response to perfusion with either NaCl or liver extract. We conclude that, under the conditions of the present study, the intestinal phase of gastric acid secretion was not accompanied by an increase in serum gastrin concentration.

Abnormal Gastric Function in Longstanding, Insulin-Dependent Diabetic Patients

We evaluated gastric function in 8 longstanding, insulin-dependent diabetic patients with nausea and recurrent vomiting, as well as in 10 asymptomatic diabetic patients and 11 nondiabetic subjects. Gastric vagal function was assessed by measuring the gastric acid secretory response to sham feeding. Normal subjects secreted 17.2 ± 3.1 meq/hr, whereas diabetic patients with, or without, vomiting secreted 5.4 ± 1.4 and 6.4 ± 2.0 meq/hr, respectively (P From these studies we conclude that many patients with longstanding insulin-dependent diabetes have (a) reduced acid secretory responses to sham feeding, suggesting vagal neuropathy; (b) normal acid secretory responses to infused food, despite an enhanced serum gastrin response; and (c) delayed gastric emptying. These abnormalities occur both in diabetic patients with nausea and vomiting and in asymptomatic diabetic patients.

Sensory functions of the liver--a review

In this paper we critically review anatomic, electrophysiological, physiological, and behavioral evidence for neural receptors in the liver. Several lines of evidence suggest that the afferent innervation of the liver may be substantial, although few anatomic studies have directly addressed the question of an hepatic sensory supply. On the other hand, there is convincing functional evidence for a variety of hepatic sensory receptors. Hepatic osmo-, ion, and baroreceptors, sensitive to changes in the osmolarity and electrolyte concentrations in blood and to variations in portal venous pressure, modulate diuresis and natriuresis. Metabolic receptors, for which the adequate stimuli have not yet been specified, influence feeding behavior and gastric acid secretion in response to alterations in hepatic metabolism associated with changes in the supply of metabolic fuels. Directions for future research are suggested and general conclusions about the role of hepatic receptors in homeostasis are discussed.

Inhibition by metiamide of secretagogue-induced gastric acid secretion in the conscious Heidenhain pouch rat.

1. The inhibition by metiamide of gastric of gastric acid secretion in response to histamine, pentagastrin and bethanechol has been investigated in the conscious Heidenhain pouch rat. 2. Histamine alone stimulated only a low rate of acid secretion. This response was markedly potentiated in the presence of mepyramine. 3. Metiamide at a dose of 0.15 mumole . kg-1 . min-1 I.V. significantly inhibited the acid secretory responses to histamine (in the presence of mepyramine) and pentagastrin. In each case the inhibition of acid output was the result of a significant decrease in both secretory volume and acid concentration. 4. Metiamide at a dose of 0.15 mumole . kg-1 . min-1 I.V. did not inhibit bethanechol-stimulated acid secretion. Increasing the dose of metiamide to 1.0 mumole . kg 1 . min-1 I.V. did produce a significant inhibition. In contrast with histamine and pentagastrin, metiamide inhibited bethanechol-stimulated secretion only by reducing acid concentration; there was no significant decrease in the gastric secretory volume. 5. It is concluded that these results are consistent with the view that histamine and pentagastrin share a common pathway in stimulating gastric acid secretion in the rat. The role of histamine in the control of bethanechol-stimulated acid secretion remains unclear.

Effect of duodenal fat on plasma levels of gastrin and secretin and on gastric acid responses to gastric and intestinal meals in dogs

The effects of duodenal instillation of sodium oleate (10 mmoles per hr) on plasma levels of gastrin and secretin and on gastric acid secretion in response to gastric and intestinal meals were determined. Four dogs prepared with a septum between stomach and duodenum were provided with a special cannula that allowed separate access to the stomach or duodenum. Each dog received a 10% liver extract meal introduced either into the stomach (gastric phase) or into the duodenum (intestinal phase). Sodium oleate administered during the gastric phase caused approximately a 30% reduction in plasma gastrin level and a 25% inhibition of gastric acid secretion. Sodium oleate given during the intestinal phase completely abolished the plasma gastrin response and resulted in a 75% inhibiton of gastric acid secretion. Plasma secretin levels were not changed during the gastric phase or the intestinal phase by instillation of sodium oleate. These results show that fat in the duodenum is a potent inhibitor of gastrin release and gastric acid secretion; the intestinal mechanism involved does not appear to affect plasma secretin concentrations.

Histamine and insulin dose-response studies of gastric secretion in Indian control subjects and patients with duodenal ulcer in the Ganges delta.

The gastric secretory responses to various doses of histamine and insulin have been studied in 11 control and 12 duodenal ulcer subjects belonging to the Ganges delta of India where the incidence of duodenal ulcer disease is known to be high. A dose of 0.04 mg/kg body weight of histamine acid phosphate was sufficient to produce peak gastric acid output both in the control and duodenal ulcer subjects. However, a dose as low as 0.025 U insulin/kg body weight was enough to produce peak rates of gastric acid output in duodenal ulcer subjects, whereas in the controls a minimum dose of 0.05 U insulin/kg body weight was sufficient. A greater proportion of the duodenal ulcer patients also showed a peak acid secretory response in the first hour after administration of insulin. Furthermore, increasing doses of insulin in this population did not produce lower levels of blood glucose but did produce increasingly high acid output as subjects do in the West. K values derived from the intravenous glucose tolerance test showed that 75% of duodenal ulcer patients and 54% of the controls had variable degrees of intolerance to glucose. Gastric acid secretion in response to a bolus of 50 ml 50% intravenous glucose was also studied in a separate group of 16 duodenal ulcer and 13 control subjects. A sharp rise in the volume, titratable acidity, and total acid output was observed in the early part of the fourth hour in the control and duodenal ulcer subjects. In a separate group of controls a bolus of intravenous hypertonic saline produced no such increase in gastric acid secretion.

Gastric acid secretion in response to liver extract and to mixtures simulating its content of total and free amino acids

GASTRIC ACID SECRETION IN RESPONSE TO LIVER EXTRACT AND TO MIXTURES SIMULATING ITS CONTENT OF TOTAL AND FREE AMINO ACIDS. E. J. Feldman, R. Melendez, and M. I. Grossman, VA Wadsworth Hospital Center, Los An 1 C lff i Liver extract (LE) is a commonly !~e?&.f&la$no~* gastric acid secretion. The purpose of this study was to determine whether the acid secretory response to LE could be mimicked by giving a mixture of amino acids simulating those found in LE. Amino acid analysis of LE showed that about 50% by weight is amino acids (AA) and that one-half of this amount is in the form of free amino acids (FAA). In four dogs with gastric fistulas, using the intragastric titration method, dose response studies were carried out with LE and with mixtures of amino acids that matched the total (AA) or the free (FAA) amino acid composition of LE. All solutions were adjusted to pH 7.0 and osmolality to 290 mOsm kg-l. At all doses of LE studied (.16X, .32%, .63X. 1.3% and 2.5%), the total AA mixture and the FAA mixture stimulated secretion to the same degree as LE. LE cont., %(gm dl-1) .16% .32X .63% 1.3% 2.5% Ht secretion, am101 h-l

Human newborn hypergastrinemia: an investigation of prenatal and perinatal factors and their effects on gastrin.

Summary: Because gastrin is a potent gastric acid stimulus and gastric acid secretion begins soon after birth, we measured umbilical cord serum gastrins. We also examined multiple factors present during the gestation, labor, delivery, and immediate postpartum period to see what effect, if any, these might have on the serum gastrins. Two groups were studied: 217 newborn infants and 802 adults without Zollinger-Ellison syndrome. The newborns' median serum gastrin was 100 pg/ml compared to the adult median of 39 pg/ml. The newborn mean was 135 pg/ml and the corresponding adult value was 40 pg/ml (P < 0.001). Twenty-nine newborns had gastrin determinations greater than 200 pg/ml; five were greater than 500 pg/ml. All adult values were less than 200 pg/ml. Thirty-five neonatal and maternal factors were analyzed to determine their effect on the gastrin levels found. No factor was found to have a significant effect except that Negro infants and maternal sickle cell trait were found to be associated with increased values. Nineteen maternal medications were also evaluated. None, including oxytocin and atropine, were found to have any effect. Serum gastrin levels continued to be elevated at hour 4 (x = 80 pg/ml) and hour 8 (x = 72 pg/ml) of life. The newborns secreted small amounts of gastric acid in response to this stimulus (range = 0.010 to 0.022 mEq/kg/hr). Speculation: During the transition to extrauterine life, the fetus is exposed to many varied stimuli. Increased vagal activity and catecholamine secretion are two physiologic reactions which occur in response to these stimuli. Both of these are known to stimulate gastrin release from G cells during extrauterine life and may account for the increased levels found at the time of delivery. The elevated gastrin levels found after birth may also be in response to these factors; however, decreased metabolism may play a role too. It is known that the kidney is the major site for gastrin metabolism in adults. The newborn kidney may not be capable of rapidly metabolizing the large gastrin load presented to it during these first hours of extrauterine life. Continued high secretion of gastrin by the G cell may also play a role in the elevated serum levels found. The low gastric acid secretion in response to these high gastrin levels may be due to decreased parietal cell responsiveness during this period of life. Decreased parietal cell mass could also be responsible. Finally, if the predominant gastrin molecule was not the G-17 moiety, decreased acid secretion would be expected.

Gastric acid secretion after chemical sympathectomy

Adrenergic nerve terminals in several organs are selectively destroyed by 6-hydroxydopamine (6-OHDA) resulting in a chemical sympathectomy that is reversible. In this study the acute and chronic effects of 6-OHDA on gastric mucosa and acid secretion were evaluated. Four dogs were given 6-OHDA (40 mg/kg, intravenously). Gastric biopsies were taken before treatment and biweekly thereafter and were analyzed by fluorescence microscopy (Hillarp-Falck). Degeneration of adrenergic nerve terminals in the mucosa was complete at 1 week. Early regeneration was noted at 3 weeks and appeared to be complete at 9 weeks. In another group of seven dogs with a gastric fistula, dose-response curves to pnetagastrin (PPG, 0 to 5 microgram/kg/hr) were determined. Then 6-OHDA (40 mg/kg) was given to these dogs and secretory studies were repeated weekly thereafter for 8 weeks. After 6-OHDA administration, acid secretion increased in response to submaximal doses of PPG, whereas maximal secretion was unchanged. The peak increase occurred the second week; thereafter secretion gradually returned to control values. We conclude that chemical sympathectomy (6-OHDA) increases gastric acid secretion in response to submaximal PPG stimulation. This increase correlates well with the 6-OHDA--induced degeneration of adrenergic terminals in the mucosa. These data suggest that the adrenergic innervation of the stomach has an inhibitory effect on the control of acid secretion in the dog.

Gastric response to meat extract stimulation in patients with gastroduodenal ulcer and patients after vagotomy or antrectomy.

Gastric acid secretion basally and in response to intragastric meat extract instillation or to tetragastrin, and circulating gastrin concentration basally and after meat extract stimulation were studied in 67 patients with gastroduodenal ulcer, 30 patients after highly selective vagotomy or selective vagotomy for duodenal ulcer, 12 patients after antrectomy for or gastric ulcer and 10 control subjects. Circulating gastrin concentration increased significantly after meat extract stimulation in control subjects, patients with ulceration and patients after highly selective vagotomy, and acid secretion in each group was increased significantly above basal level. In patients after selective vagotomy, significant increase of circulating gastrin concentration was observed, but it was not associated with significant increase of acid secretion. After antrectomy, neither gastrin nor acid secretion increased significantly after meat extract stimulation. In conclusion, present study suggested that (1) gastric acid secretion in response to intragastric meat extract is chiefly affected by the responsiveness of oxyntic cells and release of antral gastrin and that (2) the presence of the antrum is almost essential for acid secretion after a test meal, and release of duodenal gastrin after antrectomy would not be so potent biologically as to result in an acid secretion.

Comparison of vagal and meat stimulation on gastric acid secretion and serum gastrin.

The gastric acid secreted per unit of serum gastrin concentration or per unit of gastrin delivered to the gastric mucosa was significantly greater during electrical vagal stimulation than during stimulation by meat extract in the pyloric antrum. There was no significant difference in the concentrations of big, big gastrin or Components I and II in gastric venous serum during the two forms of stimulation. There were significantly greater concentrations of Components II and IV in gastric venous serum during meat extract stimulation than during vagal stimulation. The gastrin in gastric venous serum when meat extract was in the pyloric antrum was comprised of Component IV in addition to Component III whereas gastrin in extracts of cat antral mucosa was predominantly Component III. Gastric acid secretion in response to vagal stimulation was greater than can be accounted for by the action of gastrin alone and cannot be explained by differences in the known gastrin variants in the circulation during the two forms of stimulation.

Effects of chronic hypoxia on canine gastric secretion

Interdigestive gastric acid output and acid secretory response to histamine, insulin, and pentagastrin were studied in five dogs before and after creation of a right to left extracardiac vascular shunt. The arterial PO 2 decreased from 81.5 ± 5.5 mm Hg to 39.8 ± 6.0 mm Hg postoperatively with no change in arterial pH or PaCO 2. Basal (interdigestive) acid output increased from 1.19 ± 0.26 mEq/hr to 4.97 ± 0.81 mEq/hr postoperatively. Acid secretory response to insulin was increased after the induction of chronic hypoxia. Increased sensitivity to pentagastrin was also observed although parietal cell mass (maximum histamine-stimulated output) was unchanged postoperatively. Changes in acid secretory response and PaO 2 were present at one week and were sustained through twelve weeks after shunting. Chronic hypoxia resulted in gastric acid hypersecretion secondary to enhanced sensitivity of the parietal cell to a combination of neural and humoral stimuli.

Bromocriptine potentiation of gastric acid secretion in cats.

Bromocriptine administered both orally and intravenously potentiated gastric acid secretion in response to submaximal pentagastrin stimulation in cats. Bromocriptine did not increase the maximum acid secretion in response to pentastrin, not did it stimulate basal acid secretion. Potentiation was observed in normal and vagotomized animals which precludes involvement of the vagi in the response. The mechanism of action of this compound on the stomach does not appear to be mediated through stimulation of dopaminergic receptors as no potentiation was observed with dopamine infusions. It is argued that the bromocriptine potentiation of gastric acid secretion may be a demonstration of 5-hydroxytryptamine or alpha-adrenergic antagonism. However, the potentiation observed with daily oral bromocriptine treatment had disappeared by the eighth day and may correlate with the disappearance of gastric side effects noted in patients on bromocriptine treatment.

Metiamide Inhibits Canine Gastric Acid Secretion Evoked by Sham Feeding

A continuous intravenous infusion of metiamide markedly inhibited the gastric acid secretory response to sham feeding in two dogs provided with Pavlov pouches and gastric fistulae. The results show that an antagonist of histamine H2-receptors is capable of inhibiting a vagally activated secretion evoked by sham feeding, which may be considered a physiological vagal stimulus.

Gastric acid secretory responses of acute gastric fistula preparation in anesthetized young chickens.

A reliable technique which permits quantitative determination of the gastric acid secretory responses to drugs was developed in anesthetized young chickens.

Gastric Acid Secretory Responses to Graded Intravenous Doses of Histamine in Hookworm Anemia

Dose-response curves for the effect of continuous infusion of histamine on gastric acid secretion were obtained in 10 patients with iron deficiency anemia due to hookworm infection. Each patient was studied with 4 doses (40, 60, 80 and 100 mug/kg/h) of histamine acid phosphate administered for 3 h, on separate days, in random fashion. The acid output increased with the dose of histamine, the maximal acid output was reached in all patients at the dose of 100 mug/kg/h. The dose of histamine when calculated according to body weight correlated well with the maximal acid output; the absolute dose of histamine had no correlation with the maximal acid response. The dose-response curve of stimulated acid output in anemia patients was much flatter than in control patients.