Food-stimulated Acid Secretion Research Articles

Role of Aggressive Factors in the Pathogenesis of Peptic Ulcer Disease

Acid and pepsin are the major aggressive factors believed to play a role in the pathogenesis of peptic ulcer disease. On the average, patients with duodenal ulcer disease have higher than normal basal, nocturnal, and pentagastrin-stimulated acid secretion. Food-stimulated acid secretion, however, is normal in duodenal ulcer patients. The reason for higher basal and nocturnal acid secretion is not known but may be secondary to higher than normal basal serum gastrin concentrations in duodenal ulcer patients. Average serum pepsinogen levels also are higher than normal in patients with duodenal ulcer disease, suggesting that luminal pepsin concentrations also are higher. Patients with gastric ulcers have either normal or lower than normal acid secretion. This suggests that factors other than acid and pepsin may play a role in causing gastric ulcers. Reflux of bile and pancreatic juice into the stomach of patients with gastric ulcers has been suggested as one of the aggressive factors playing a role in the development of gastric ulcers.

Effect of terbutaline, a β2-adrenoreceptor agonist, on gastric acid secretion and serum gastrin concentrations in humans

Because β-adrenoreceptor agonists inhibit gastrinstimulated gastric acid secretion in animals, we postulated that the β2-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 < 0.005), even though terbutaline increased serum gastrin levels (p < 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, β2-adrenoreceptor agonists enhance gastrin release while at the same time inhibiting gastrin-stimulated acid secretion in humans.

2-Oxo-1,8-naphthyridine-3-carboxylic acid derivatives with potent gastric antisecretory properties.

The syntheses of 2-oxo-1,8-naphthyridine-3-carboxylic acid derivatives having potent gastric antisecretory properties in the pyloric-ligated (Shay) rat model are described. Two of the more potent compounds tested that were selected for more detailed dose-response evaluation were 4-amino-1-ethyl-1,2-dihydro-2-oxonaphthyridine-3-carboxylic acid ethyl ester (35) and 1-ethyl-1,2-dihydro-7-methyl-4-(4-methyl-1-piperazinyl)-2- oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester (77). These compounds lowered total acid output in the rat in a dose-related fashion. Both compounds were more potent than cimetidine when tested in the rat. Both 35 and 77 showed inhibitory activity in food-stimulated acid secretion in the Pavlov-pouch, conscious dog. The mechanism of action for this series is not known. Details of structure-activity relationships are described.

O-311 - Gastrin mediation of food-stimulated acid secretion in the rat : Inhibition by monoclonal antibody to gastrin(28.2)

O-311 - Gastrin mediation of food-stimulated acid secretion in the rat : Inhibition by monoclonal antibody to gastrin(28.2)

Somatostatin inhibits gastric acid secretion after gastric mucosal prostaglandin synthesis inhibition by indomethacin in man.

The inhibitory effect of indomethacin, 200 + 200 mg administered per os over 24 hours, on the prostaglandin E2 generative capacity of gastric mucosal tissue was determined in healthy male volunteers. The effect of prostaglandin synthesis inhibition on somatostatin induced suppression of food-stimulated acid secretion was tested. Peptone meal stimulated acid secretion was quantified in five healthy volunteers by intragastric titration with and without indomethacin pretreatment. Somatostatin doses of 200, 400, and 800 pmol/kg/h each significantly inhibited the peptone stimulated acid output. Indomethacin treatment, resulting in 90% inhibition of prostaglandin E2 synthesis, did not affect glucose- or peptone-stimulated acid output or modify the inhibitory action of somatostatin. Clinically, acid inhibition by somatostatin has been used to treat bleeding peptic ulcers. Ulcer haemorrhage may be preceded by an excessive use of drugs that inhibit prostaglandin synthesis such as aspirin or other non-steroidal anti-inflammatory agents. Recent observations in the rat indicate that prostaglandins mediate the inhibitory action of somatostatin on gastric acid secretion. The present results suggest that prostaglandins are not required for inhibition of gastric acid secretion by somatostatin in man.

Misoprostol: inhibits food-stimulated gastric acid secretion

Misoprostol: inhibits food-stimulated gastric acid secretion

Inhibition of food stimulated acid secretion by misoprostol, an orally active synthetic E1 analogue prostaglandin.

The effect of 200 micrograms misoprostol (a synthetic prostaglandin E1 analogue) on food stimulated intragastric acidity has been monitored over a 9 h period in 16 normal volunteers. Misoprostol caused a significant inhibition of intragastric acidity for 2 h post-dosing, but no significant effect was seen thereafter on either basal or food stimulated acidity.

Effect of indomethacin on gastric acid and bicarbonate secretion in humans

The role of endogenous prostaglandins in the physiologic regulation of gastric secretion is unclear. We evaluated the effect of indomethacin, an inhibitor of endogenous prostaglandin synthesis, on basal gastric secretion in humans using a two-component model for calculating gastric acid and bicarbonate secretion. After a control, gastric secretory study, 11 healthy volunteers were given 50 mg of indomethacin orally every 8 h for a total of 10 doses, after which the gastric secretory experiment was repeated. Indomethacin significantly (p < 0.05) increased basal gastric juice volume, hydrogen ion concentration, osmolality, and acid output. Indomethacin increased acid secretion significantly (from 4.9 ± 1.2 to 7.4 ± 1.7 mmol/75 min, p < 0.02) without affecting gastric bicarbonate secretion (control 2.7 ± 0.8, indomethacin 3.0 ± 0.7 mmol/75 min; p > 0.05). The increase in basal acid secretion after indomethacin administration was quite variable from subject to subject and was unaccompanied by significant changes in basal serum gastrin concentrations. Unlike basal acid secretion, indomethacin had no significant effect on acid secretion stimulated by intragastric infusion of homogenized food. Moreover, indomethacin did not prevent intravenous somatostatin 14 from inhibiting food-stimulated acid secretion, in contrast to a previous study in rats in which indomethacin blocked the inhibitory effect of somatostatin on acid secretion. Assuming the effect of indomethacin is due to reduced endogenous prostaglandin synthesis, we conclude that (a) in some individuals endogenous prostaglandins suppress basal acid secretion by a mechanism independent of the hormone gastrin; (b) endogenous prostaglandins play little, if any, role in the regulation of basal bicarbonate secretion by the stomach; and (c) endogenous prostaglandins do not regulate food-stimulated acid secretion, nor do they mediate the inhibitory effect of somatostatin on gastric acid secretion in humans.

Tiotidine, a new long-acting histamine H2-receptor antagonist: Comparison with cimetidine

The effects of tiotidine, a new histamine H2-receptor antagonist, and cimetidine on food-stimulated gastric acid secretion were evaluated in duodenal ulcer patients. Homogenized steak meals were infused immediately after, 1 h after, 5 h after, and 10 h after an oral dose of medication, and food-stimulated acid secretion was measured by in vivo intragastric titration. Tiotidine and cimetidine had a similar onset of action; however, tiotidine was more potent and had a longer duration of effect. Increased potency was demonstrated by the fact that from 1 to 2 h after medication 150 mg tiotidine inhibited acid secretion to approximately the same extent as did 300 mg cimetidine, and by the fact that for a given percent inhibition of acid secretion, plasma tiotidine concentration was eight to nine times lower than plasma cimetidine concentration. Longer duration of effect was demonstrated by the fact that from 5 to 7 h after medication, acid secretion was inhibited by 80% and 97% with 150 and 300 mg tiotidine, respectively, whereas 300 mg cimetidine inhibited acid secretion by only 22%. Also, 10–12 h after medication, 150 and 300 mg tiotidine inhibited acid secretion by 22% and 53%, respectively, while 300 mg cimetidine had no inhibitory effect. The long duration of effect was due in part to increased potency and in part to a plateau in plasma concentration of tiotidine, which was maintained from 2 to 6 h after medication. Neither tiotidine nor cimetidine had a significant effect on food-stimulated gastrin release or gastric emptying of a nonabsorbable marker.

Gastroenterology: An Annotated Bibliography of Recent Literature

Gastroenterology: An Annotated Bibliography of Recent Literature

Effect of Selective Proximal Vagotomy on Food-Stimulated Gastric Acid Secretion and Gastrin Release in Patients With Duodenal Ulcer

We studied effects of selective proximal vagotomy on food-stimulated acid secretion and gastrin release in 7 duodenal ulcer patients. Food-stimulated acid secretion was evaluated by sham feeding patients and by infusing food directly into their stomachs. Vagotomy reduced sham feeding-stimulated acid secretion from 28.2 +/- 4.6 to 1.2 +/- 0.7 meq/hr (95% reduction) whereas infused food-stimulated secretion was decreased from 36.1 +/- 4.6 to 17.9 +/- 5.5 meq/hr (50% reduction). In contrast to the reductions in acid secretion, the gastrin response to infused food doubled after surgery. Although selective proximal vagotomy reduced the rate of acid secretion in response to infused food and also reduced by 64% the peak secretory capacity (peak acid output to pentagastrin), fractional secretion (i.e., the secretion rate in response to infused food expressed as a percentage of the peak secretory capacity) increased significantly after vagotomy from 63 +/- 7% to 91 +/- 11%. This increased fractional secretion in response to infused food was probably a result of exaggerated gastrin release after vagotomy.

Food-stimulated acid secretion measured by intragastric titration with bicarbonate in patients with duodenal and gastric ulcer disease and in controls.

Gastric acid secretion stimulated by a normally eaten beefsteak meal was measured for 4 h in 16 patients with duodenal ulcer disease (DU), in 9 patients with gastric ulcer disease (GU), and in 14 controls by intragastric titration with bicarbonate to a constant pH 5.5. Reproducibility of the method investigated in 6 DU and in 5 controls gave similar acid secretory values (var. coeff. = 7.5%). DU produced acid on a higher level and with longer duration after food than controls and GU (p less than 0.001). Apart from the second half of the first hour after food, when the acid secretion was higher in controls than in GU (p less than 0.025), there was no significant difference in acid output after food between GU and controls. Maximum gastrin values and 'total gastrin output' after food were significantly higher in GU than in controls, but these differences were not significant between GU and DU and between DU and controls. Fasting gastrin and gastrin levels after food were not correlated to basal acid output or acid output after pentagastrin or food in any of the groups. The maximal acid output after food was higher than the peak acid output after pentagastrin in controls, DU and GU. The relation between food- and pentagastrin-stimulated acid output was not statistically significantly different between the three groups. Instead, acid secretion after food was well correlated to acid secretion after pentagastrin in controls, DU and GU (r = 0.85).

Antral Denervation in Parietal Cell Vagotomized Dogs

In ten Heidenhain pouch (HP) dogs who previously had undergone parietal cell vagotomy (PCV) with gastroduodenostomy, the antral nerves were cut, and the PCV thus converted to a selective gastric vagotomy (SGV). Mean gastric emptying rate was unaffected but antral motility changed considerably, the stomach became big and slack, and the emptying of a food-barium meal became purely passive. While the duodenal bulb was often filled with gastric content before antral denervation, this happened very seldom afterwards. Fasting, food-stimulated and 24-hour HP acid secretion increased significantly after denervation, but this was not accompanied by any significant changes in serum gastrin concentration. This indicates that other factors than gastrin must be responsible for the increased HP acid response to a meal after antral denervation.

Effect of chronic antacid ingestion on serum gastrin and gastric secretion

Basal gastrin and acid secretion, and histamine- and food-stimulated acid secretion were examined before and after 6 weeks of regular antacid consumption by 20 normal volunteers, in order to test the hypothesis that regular use of antacids produces gastrin cell hyperplasia, altered gastrin inhibition by acid, and gastric hypersecretion. We found no differences in fasting serum gastrin, basal or maximal histamine-stimulated acid, or acid output in response to a protein meal after consumption of commercial antacids with or without calcium carbonate. The results suggest that normal subjects do not acquire functional hyperactivity of the gastrin mechanism after a period of regular antacid use.

Effect of Secretin on Gastric Function in Normal Subjects and in Patients with Duodenal Ulcer

The effect of constant intravenous infusion of secretin in doses of 0.25, 0.50, 1.50, and 3.0 mug per kg per hr on meal-stimulated acid secretion was measured in vitro titration to pH 5.0. The pattern and degree of secretin inhibition of food-stimulated acid secretion depended on when the secretin infusion was begun, the effect being more pronounced when the secretin was begun 1 hr before the test meal than when the meal and secretin infusions were begun simultaneously. Inhibition of acid secretion in normals was approximately the same as in 2 patients with pancreatic exocrine insufficiency who could secrete only small amounts of pancreatic bicarbonate in response to secretin. Secretin in dose of 0.25 and 0.5 mug per kg per hr inhibited acid secretion only slightly, whereas 3.0 mug per kg per hr completely stopped acid secretion. Inhibition of acid secretion by secretin was similar in controls and in patients with duodenal ulcer. Secretin also reduced the rise in serum gastrin concentration after the meal, and delayed gastric emptying; both responses were approximately the same in normals and in duodenal ulcer patients. Secretin inhibited basal gastric acid secretion but had no consistent effect on basal serum gastrin concentration.

EFFECT OF FEMALE SEX HORMONES AND ADRENOCORTICOTROPHIN ON FELINE GASTRIN AND GASTRIC SECRETIONS

The effect of female sex hormones and adrenocorticotrophin (ACT) gas trin and gastric secretions were studied in cats. ACT did not significantly alter the basal serum gastrin response from preestimation values (p greater than .05). The secretion of acid was not significantly affected either (p greather than .05). less pentapeptide stimulation significantly (p less than .01) decreased pepsin output while food stimulation had no effect on pepsin output. Food stimulation did however significantly increase acid secretion (p less than .05). The administration of female sex hormones significantly (p less than .01) decreased fasting serum gastrin concentrations and the acid respons e to food stimulation but not the acid response to gastrin pentapeptide stimulation. The protein content of gastric secretions was unchanged during treatment with female sex hormones. The results suggest that the decrease in food-stimulated acid secretion is the result of a decrease in gastrin concentration while the acid secretory mechanism is unchanged.

The mechanism whereby growth hormone-release inhibiting hormone (somatostatin) inhibits food stimulated gastric acid secretion in the cat.

Growth hormone-release inhibiting hormone (somatostatin) inhibits the gastric acid response to food in concious cats. We have confirmed that this tetradecapeptide blocks the food stimulated gastrin release. However, the inhibition of gastrin release is delayed relative to that of acid secretion, &howing that the inhibition of food stimulated acid secretion is by primary effect on the acid secretory mechanism. No evidence was found of potentiation of either the gastric acid output or serum concentration of gastric in response to food.

The effect of an H2-receptor antagonist on food-stimjlated acid secretion, serum gastrin, and gastric emptying in patients with duodenal ulcers. Comparison with an anticholinergic drug.

The purpose of the present series of experiments was to measure and compare the effects of an anticholinergic drug (isopropamide) and an antagonist of the histamine H2 receptor (metiamide) on food-stimulated acid secretion. Patients with duodenal ulcers were stimulated by a steak meal, and acid secretion was measured by in vivo intragastric titration. The largest dose of isopropamide that can be taken clinically without producing intolerable side effects (maximum tolerated dose) suppressed food-stimulated acid secretion by 35%. By contrast, metiamide in a 400-mg dose produced no side effects and almost completely abolished food-stimulated acid secretion. A dose-response curve revealed that a 50-mg dose of metiamide was required to suppress food-stimulated acid secretion by 50%. Further studies showed that metiamide and isopropamide are additive in suppressing food-stimulated acid secretion, and that metiamide has no effect on serum gastrin concentration or on gastric emptying.

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.