Stimulation of pyruvate carboxylation by gastric secretagogues

Summary Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa.This investigation was supported by Consejo de Desarrollo Científico y Humanístico de la Universidad del Zulia, and by CONICIT Grant S1-0455.     

Inhibitory effect of ouabain on in vitro and in vivo gastric acid secretion in the frog and the rat

The in vitro and in vivo effects of ouabain on gastric acid secretion in the frog and the rat, the 2 species known to have different sensitivity to ouabain, were studied. It was found that ouabain was a potent inhibitor of histamine-stimulated acid secretion in the isolated frog gastric mucosa. Ouabain administered i.v. at dose levels far below the lethal range also produced a marked and significant reduction of histamine-stimulated gastric acid secretion in the anesthetized frogs and rats. It is considered that the inhibitory effect of ouabain on acid secretion could be partly related to its specific antagonizing action on the Na+ -K+ -ATPase in the gastric mucosa.     

Inhibitory effect of ouabain on in vitro and in vivo gastric acid secretion in the frog and the rat

Summary The in vitro and in vivo effects of ouabain on gastric acid secretion in the frog and the rat, the 2 species known to have different sensitivity to ouabain, were studied. It was found that ouabain was a potent inhibitor of histamine-stimulated acid secretion in the isolated frog gastric mucosa. Ouabain administered i.v. at dose levels far below the lethal range also produced a marked and significant reduction of histamine-stimulated gastric acid secretion in the anesthetized frogs and rats. It is considered that the inhibitory effect of ouabain on acid secretion could be partly related to ist specific antagonizing action on the Na⁺-K⁺-ATPase in the gastric mucosa.     

Gastric secretion during anaesthesia and its inhibition by metiamide and other drugs.

The histamine H2-receptor antagonist, metiamide, inhibits the acid gastric secretion produced by chloralose-urethane anaesthesia in dogs carrying gastric cannulae chronically. This secretion is also prevented by atropine and hexamethonium. "Spontaneous" gastric secretion of vagal origin in conscious dogs is also blocked by metiamide.     

Modification of the action of pentagastrin on acid secretion by botulinum toxin.

I.v botulinum toxin after 60-90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin.     

Hydrochloric acid secretion of fetal rat gastric mucosa]

In Rat, spontaneous secretion of hydrochloric acid by gastric mucosa takes place before birth. From day 20 of gestation until birth, the pH of gastric content markedly decreases, reaching 3 pH-units in newborns. During this period, Cl- concentration in gastric juice increases, while p-CO2 remains constant.     

Stimulation of gastric secretion by prostaglandin F2 alpha in rats.

In rats with chronic gastric fistulas, prostaglandin F2 alpha stimulated the gastric acid secretion in graded doses of 50, 100, 200 and 400 microgram/kg b.wt, while higher doses above 1 mg/kg b.wt tended to inhibit significantly. The gastric antisecretory effect of prostaglandin E1 could not be altered or modified by subsequent treatment of prostaglandin F2 alpha, while the latter alone without any prior treatment of the former, stimulated output of gastric juice, HCl and pepsin without significantly affecting the concentration of these components.     

Immunological blocking of exogenous and endogenous secretin in the dog.

In mongrel dogs with chronic gastric and duodenal fistula the biological activity of secretin on exocrine pancreatic secretion could be blocked by preincubating the secretin injected with rabbit antisecretin antibody. In addition, the activity of endogenous secretin released by acid was markedly reduced by application of antibody. Since no such effect was observed after testmeal stimulation, secretin is most probably not released in a significant amount by the liquid meal used in this experiment.     

Modification of the action of pentagastrin on acid secretion by botulinum toxin

Summary I.v. botulinum toxin after 60–90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin.Acknowledgment. We are grateful to the generosity of Dr Edward J. Schantz, Food Research Institute, University of Wisconsin, for the botulinum toxin used. — This research was supported by NIH grant 1 RO1 AM 17125, The Secretion of Pepsin.     

Isolation of a hexaprenylhydroquinone sulfate from the marine sponge Dysidea sp. as an H,K-ATPase inhibitor

A hexaprenylhydroquinone sulfate has been isolated as an H,K-ATPase inhibitor from a marine sponge Dysidea sp. It also inhibited phospholipase A2 as well as secretion of gastric acid in rats.     

Synthesis and some characteristics of [13C]-specially enriched tetragastrin and the related compound

[13C]-enriched tetragastrin and the related compound were synthesized in solution. Conversion of S-[13C]methylated tetragastrin to the enriched tetragastrin gave 10.5 ppm upfield chemical shift of Cepsilon resonance. The potency of the synthetic tetragastrin to stimulate gastric acid secretion was virtually identical with that of pentagastrin (ICI).     

Molecular mechanisms in therapy of acid-related diseases

Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists. Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007     

Infusion of a novel peptide, PHI, in man. Pharmacokinetics and effect on gastric secretion

PHI, infused in man, achieved plateau plasma levels of 297 pmoles/1. The plasma half life was 3.1 min, metabolic clearance rate was 16.4 ml/kg/min and estimated volume of distribution was 73.2 ml/kg. No subjective side effects were noted during the infusion and there was no significant alteration in submaximal pentagastrin stimulated gastric acid or pepsin secretion.     

Neural discharge can be modulated by carotid arterial injection of gastrin-17 in rat hypothalamic paraventricular nucleus

Neural discharge in the hypothalamic paraventricular nucleus (PVN) was examined after gastrin-17 injection into the carotid artery in anesthetized rats. Neural discharge was increased by gastrin-17 injection into the carotid artery close to the cranium, and the response due to the gastrin was dose-dependent. No discharge response was seen when gastrin was injected into the jugular vein. These results suggest that gastrin circulating in the arterial blood can penetrate the blood brain barrier, and modulate neural PVN activity which is responsible for gastric acid secretion.     

Einbau von Schwefelwasserstoff in Verbindungen des Photosynthesestoffwechsels

Summary The presence of sulphide in the reaction mixture of the Ru-DP carboxylation leads to the synthesis of phospho-thioglyceric acid.     

Inhibition in the rat of gastric acid secretion and cyclic AMP analogs accumulation in vitro by somatostatin.

Various somatostatin (S) analogs exhibited similar degree and similar, or shorter, duration of inhibition of basal gastric acid secretion as S in the unanesthetized rat and similar, or less, inhibition of the cyclic AMP accumulation induced by prostaglandin E2 in the rat anterior pituitary in vitro. With the analogs examined, the gastrointestinal and pituitary receptors appear to exhibit generally similar recognition specificity with the differences within the gastro-intestinal activities reflecting duration of availability rather than receptor affinity.     

Urogastrone-epidermal growth factor is trophic to the intestinal epithelium of parenterally fed rats

The weight of the stomach, small intestine and colon and the mucosal crypt cell production rate of these tissues were significantly decreased after 10 days on an isocaloric TPN diet when compared to orally fed controls. Continuous infusion of recombinant beta urogastrone, at a dose below that needed to inhibit gastric acid secretion, largely prevented this decrease in crypt cell production rate and gastrointestinal tissue weights.     

Stimulation of H+ ion secretion from the isolated mouse stomach by sodium fluoride

Summary The effect of sodium fluoride on H⁺ ion secretion was investigated in the isolated distended mouse stomach. It was found that sodium fluoride on its own caused dose-related stimulation of H⁺ ion secretion. Sodium fluoride did not inhibit H⁺ ion secretion induced by histamine. The possible mechanisms involved are discussed. It is considered that sodium fluoride might stimulate H⁺ ion secretion by causing histamine release and by increasing cyclic AMP formation in the intact gastric mucosa.     

Urogastrone-epidermal growth factor is trophic to the intestinal epithelium of parenterally fed rats

Summary The weight of the stomach, small intestine and colon and the mucosal crypt cell production rate of these tissues were significantly decreased after 10 days on an isocaloric TPN diet when compared to orally fed controls. Continuous infusion of recombinant beta urogastrone, at a dose below that needed to inhibit gastric acid secretion, largely prevented this decrease in crypt cell production rate and gastrointestinal tissue weights.