The Future of the Pump

The aim of the present study was to investigate whether circulating somatostatin takes part in the inhibition of gastric acid secretion induced by acidification of the antrum and the duodenal bulb. Dogs provided with chronic pouches of the antrum or the duodenal bulb, and with Pavlov pouches were used in the study. Peripheral venous somatostatin levels rose on the average to ˜36±15 pmol/1 and 20±3 pmol/1 during perfusion of the antral or bulbar pouches with 0.1 M HC1 respectively. A slight increase was also obtained on antral perfusion with solutions of pH 2.2–3 and on bulbar perfusion with solutions of pH 2.2, whereas peripheral somatostatin levels remained unchanged, when the pouches were exposed to solutions of higher pH. The increase of plasma somatostatin levels coincided in time with the release of somatostatin into the lumen of the antrum and of the duodenal bulb, which showed the same pH dependency. Also plasma gastrin levels rose during perfusion of the pouches with 0.1 M HCI, this was especially the case during perfusion of the antral pouches. Perfusion of bulbar pouches, but not of antral pouches with 0.1 M HC1 inhibited the pentagastrin (2 μg/kg/h) stimulated gastric acid secretions. Infusions of somatostatin (0.15, 0.3 and 0.6 nmol/kg/h) caused plasma somatostatin levels ˜0, 0–20 and ˜50 pmol/1 respectively. Infusions of somatostatin (0.3‐1.2 nmol/kg/h) inhibited pentagastrin stimulated (2 μg/kg/h) gastric acid secretion and 0.15 nmol/kg/h inhibited the acid secretion induced by pentagastrin (1 μg/kg/h). Thus infusions of somatostatin which inhibited pentagastrin induced acid secretion gave rise ot plasma somatostatin levels of comparable size ˜(0–50 pmol/1) to those induced by acidification of the antrum or the duodenal bulb ˜(36 and 20 pmol/1). We therefore suggest that endogenously released somatostatin may account for the inhibition of gastric acid secretion observed during acidification of the duodenal bulb, thus corresponding to the postulated hormone bulbogastrone. The existence of similar inhibitory substance of antral origin (i. e. the antral chalone) has been proposed. We also suggest that this substance corresponds to somatostatin, despite the fact that it is difficult to inhibit pentagastrin‐induced gastric acid secretion by acidification of the antrum. It is suggested that the inhibitory effect on gastric acid secretion exerted by somatostatin released from the antrum might be masked under the present experimental conditions. Thus, gastrin and perhaps also other peptides, which stimulate acid secretion, are also released by antral acidification and they might in part counteract the depressant effect on acid secretion induced by somatostatin. Furthermore, since the antral pouches were innervated, vagovagal reflexes induced by antral acidification might also influence the rate of acid secretion. The main physiological function of the acid induced antral somatostatin release might be to block the release of gastrin in response to various stimuli.

Action of tin on the secretory effect of agents which stimulate gastric acid secretion in rats

Serotonin (5-hydroxytryptamine, 5-HT) produces many changes in gastric functional parameters, including the inhibition of gastric acid secretion and changes in mucosal blood flow. Exogenous 5-HT has also been shown to induce gastric erosion. The influence of adrenalectomy on experimental lesions in the rat gastric mucosa remains controversial. The aim of this study was to see the effects of adrenalectomy on pentagastrin stimulated gastric acid secretion in anaesthetized male Wistar rats. Gastric acid was collected via cannulae placed in the stomach. 5-HT (3.5 mumol/kg, i.v.) inhibited pentagastrin stimulated acid output by 54% and produced haemorrhagic gastric lesions with a mean ulcer index of 2 +/- 0.3. Adrenalectomy prevented both 5-HT induced inhibition of gastric acid secretion and mucosal injury. The results suggest that the effects of 5-HT require an intact adrenal gland.

To evaluate the importance of the terminal carboxyl group of the oleic acid molecule in the inhibition of gastric acid secretion, 6 normal persons were stimulated twice with duodenal perfusates containing either 20 mM oleic acid or 20 mM oleyl alcohol. Oleic acid significantly inhibited the gastric acid secretion stimulated by pentagastrin (100 ng/kg/h) and increased the levels of secretin in plasma. The effect of oleyl alcohol was insignificant. It is concluded that the carboxyl group of the fat molecule has an important role in the inhibition of gastric acid secretion, and the effect could in part be attributable to the release of secretin into plasma.

The action of metiamide on histamine-, and pentagastrin-, insulin-, and meal-induced maximal gastric secretion was studied in six duodenal ulcer patients. Gastric acid secretion in tests with histamine, pentagastrin, or insulin stimulation was collected by a simple aspiration technique whereas that induced by a peptone meal was determined by the modified intragastric titration method of Fordtran and Walsh, in which acid output was measured by monitoring the rate at which 0.5 M sodium bicarbonate had to be added to keep the gastric content at the initial value of pH 5.0. Metiamide produced a dose-related inhibition of histamine-induced acid and pepsin outputs, and the dose required for 50% inhibition was about 1 mg/kg-hr. Metiamide given intravenously in a dose of 1 mg/kg-hr caused a strong and immediate inhibition of gastric acid and pepsin secretion induced by all stimuli used. Similar inhibition was observed after intragastric administration of metiamide in a single dose of 4 mg/kg. We conclude that metiamide is a very strong inhibitor of gastric acid and pepsin secretion induced by a variety of secretory stimuli and that it might deserve attention from clinicians as a side-effect-free depressant of acid secretion in the treatment of peptic ulcer disease.

Effect of genotypic differences in interleukin-1 beta on gastric acid secretion in Japanese patients infected with helicobacter pylori

The inhibitory effect of duodenal exposure to acid and hyperosmolal solutions on pentagastrin-stimulated gastric acid secretion was studied in conscious rats equipped with chronic gastric fistula and duodenal Thiry-Vella loop. The loop was challenged with saline, HCl or hyperosmolal polyethylene glycol. Gastric acid secretion was measured in samples from the gastric fistula. Gut peptide concentrations were measured in duodenal perfusates collected each 30 min, and in plasma samples collected both during stimulated acid secretion alone, and at the end of experiments in combination with luminal challenges of the loops. During pentagastrin-stimulated gastric acid secretion, luminal perfusion of the duodenal loop with acid caused inhibition of acid secretion (P < 0.001) and a prominent release of somatostatin both to the lumen (P < 0.001) and to the circulation (P < 0.05). Also, neurotensin (P < 0.01) and vasoactive intestinal peptide (P < 0.01) were released to the lumen, but not to the circulation. Upon perfusion of the duodenal loop with hyperosmolal polyethylene glycol, acid secretion was inhibited (P < 0.05) and somatostatin alone was released to the luminal side (P < 0.01). In conclusion, duodenal exposure to acid inhibits pentagastrin-stimulated gastric acid secretion and releases SOM to the circulation that may directly inhibit acid secretion. Concomitantly, somatostatin (SOM), neurotensin and vasoactive intestinal peptide are released to the lumen. Duodenal exposure to hyperosmolal polyethylene glycol inhibits acid secretion with a luminal release of SOM only. Thus, luminal acid and hyperosmolal solutions inhibit gastric acid secretion by separate mechanisms. After acid or hyperosmolal challenge, the release of SOM to the circulation indicates gastric acid inhibition in an endocrine manner, while a luminal release of gut peptides indicates a local peptide overflow that might be of importance via paracrine regulatory mechanisms in the intact animal.

The effect of intrajejunal infusion of hypertonic glucose on pentagastrin-stimulated (0.5 microgram/kg-hr) gastric acid secretion was studied in eight duodenal ulcer patients before and three to five months after truncal vagotomy. Preoperatively mean acid output was reduced from 44.0 +/- 3.1 meq H+/hr to 29.2 +/- 2.9 meq H+/hr (p less than 0.05), whereas no consistent changes were found postoperatively, suggesting that jejunal inhibition of gastric acid secretion induced by hypertonic glucose primarily is under vegal control. Furthermore, the study shows that glucose induced jejunal inhibition of acid secretion seems to be less pronouced in duodenal ulcer patients than previously found in healthy subjects.

Effect of oral and intravenous 16,16-dimethyl prostaglandin E2 in duodenal ulcer and Zollinger-Ellison syndrome patients

An increase in gastric acid secretion after resection or bypass of the small bowel has been described by several authors in man and dogs1,2,3. Furthermore, a high incidence of peptic ulcer disease has been observed in patients with small bowel resection4,5. The mechanism which induces gastric hypersecretion after exclusion of large parts of the small bowel from food passage is still poorly understood. Several authors have described hypergastrinemia after small bowel exclusion or bypass, which may be caused by either a decrease in catabolism or a diminished release of inhibitors from the small intestine6,7,8. One of the physiologically important inhibitors of gastric acid secretion may be the gastric inhibitory polypeptide (GIP) which is released from the duodenum and jejunum after food intake and shows besides its insulinotropic effect a strong inhibition of stimulated acid secretion in dogs9.

A hydrophobic amine, SCH 28080, 2-methyl-8-(phenylmethoxy)imidazo(1,2a)pyridine-3-acetonitrile, previously shown to inhibit gastric acid secretion in vivo and in vitro, was also shown to inhibit basal and stimulated aminopyrine accumulation in isolated gastric glands when histamine, high K+ concentrations, or dibutyryl cAMP were used as secretagogues. Stimulated, but not basal, oxygen consumption was also inhibited. Neutralization of the acid space of the parietal cell by high concentrations of the weak base, imidazole, reduced the potency of the drug, suggesting that SCH 28080 was active when protonated. Studies on the isolated H+,K+-ATPase showed that the compound inhibited the enzyme competitively with K+, whether ATP or p-nitrophenyl phosphate were used as substrates. In contrast, the inhibition was mixed with respect to p-nitrophenyl phosphate and uncompetitive with respect to ATP. The drug reduced the steady state level of the phosphoenzyme but not the observed rate constant for phosphoenzyme formation in the absence of K+ nor the quantity of phosphoenzyme reacting with K+. The drug quenched the fluorescence of fluorescein isothiocyanate-modified enzyme and also inhibited the ATP-independent K+ exchange reaction of the H+,K+-ATPase. Its action on gastric acid secretion can be explained by inhibition of the H+,K+-ATPase by reversible complexation of the enzyme. This class of compound, therefore, acts as a reversible inhibitor of gastric acid secretion.

The effect of intravenous infusion of L-arginine on pentagastrin-stimulated gastric acid secretion was studied in 15 duodenal ulcer patients and 12 healthy subjects. In both groups L-arginine enhanced plasma concentrations of pancreatic glucagon equally and to levels similar to those seen after a protein-rich meal and inhibited the acid response in duodenal ulcer patients and in normal subjects. The study supports previous findings suggesting that pancreatic glucagon is a physiological inhibitor of gastric acid secretion but does not support the hypothesis of a defect in this inhibitory system in duodenal ulcer patients.

Background: The effect of concomitant use of herbs and conventional drugs is not widely known because it hasn’t been a common practice especially among the elite and those resident at the urban centers but very common among the rural duelers for co-administered herbs/supplements and conventional drugs. This study was carried out to investigate the interaction between moringa oleifera and rabeprazole in gastric acid secretion. Methods: Twenty (20) adult Wistar albino rats of both sexes weighing 300-450 g were randomly allocated into four (4) groups of five (5) animals per group. Group 1 served as the control and was given normal saline without administration of acid alcohol. Animals in group 2 were given acid alcohol (0.25 ml 0f 36% HCl + 75% ethanol 0.25 ml/100 g body weight). Animals in group 3 were given 50 mg/100 g bw of Moringa oleifera 1 hour before acid alcohol was administered. Group 4 were given: Rabeprazole 20 mg /kg body weight + acid Alcohol (36% HCL 0.25 mls+ 75% Ethanol (0.25 mls). A 30% isoflorane (inhalational anesthesia) by API Manufacturer with FDA, UK, marketed by Macfes medical store, high level Markurdi, Benue State, Nigeria. And 3.5% isoflurane (of the mixture of isoflurane 30%) at 100% oxygen was soaked in a cotton wool and dropped in clean and covered plastic container, and was used to anesthetized the rats, for the purpose of the aqueous extracts administration through a gastric fistula created by a surgical procedure. 10 minutes after aqueous extracts administration, aliquot samples were collected over 4 hours. Gastric acid secretion was measured by titrating the aliquots to a phenolphthalein endpoint. Results: showed that Moringa Olefera significantly delayed the time of onset of action of rabeprazole when co-administered. Moringa alone was a better inhibitor of gastric acid secretion than moringa co-administered with rabeprazole. Conclusion: Moringa delays the time of onset of action of Rabeprazole when co-administered.

Glucagon-like peptide (GLP)-2 is formed from proglucagon in the intestinal L cells and is secreted postprandially in parallel with the insulinotropic hormone GLP-1, the latter of which, in addition, acts to inhibit gastric secretion and motility by inhibiting central parasympathetic outflow. We now studied the effect of GLP-2 on gastric secretion stimulated by sham feeding to test the hypothesis that also GLP-2 acts as an enterogastrone. Eight healthy volunteers were studied twice on separate days. They were sham fed with and without GLP-2 infused iv at a rate of 0.8 pmol/kg x min. Gastric contents were aspirated continuously by a nasogastric tube for determination of acid secretion, volume, and osmolarity. Sham feeding increased gastric acid secretion nearly 5-fold. Infusion of GLP-2 reduced incremental acid secretion by 65+/-6%, compared with saline infusion (delta8.75+/-0.37 vs. delta3.04+/-0.47 mmol x 60 min; P<0.01). Plasma concentrations of GLP-2 rose from a basal mean of 3.3+/-0.9 to a mean of 115+/-8 pmol/L (range, 57-149 pmol/L) during infusion of GLP-2 and remained at basal level during saline infusion. Plasma concentrations of GLP-1, gastrin, cholecystokinin, and secretin remained low and unchanged on both study days. We conclude that GLP-2 is a powerful inhibitor of gastric acid secretion in man. Further investigations will show to what extent GLP-2 contributes to the inhibitory effects on gastric secretion exerted by hormones from the distal small intestine, under physiological circumstances.

Inhibitory Effect of Intravenous GABA Antagonists on Gastric Acid Secretion Stimulated by Secretagogues in Rats