Measurement Of Acid Secretion Research Articles

Gastric Acid Analysis Is a Reliable and Reproducible Measure of Acid Secretion in GERD Patients Treated with Placebo or Pantoprazole

Gastric Acid Analysis Is a Reliable and Reproducible Measure of Acid Secretion in GERD Patients Treated with Placebo or Pantoprazole

Mesenchymal Transcription Factor Fkh6 Is Essential for the Development and Differentiation of Parietal Cells

The role of transcription factor forkhead homologue 6 (Fkh6) gene expressed only in gastrointestinal mesenchymes on the differentiation of gastric epithelia was analyzed by inactivating the gene by targeting disruption. Gastric mucosa exhibited hyperplasias with disordered glandular structures in the absence of gene. Measurement of acid secretion in the isolated whole stomach demonstrated that both basal and stimulated secretions were severely suppressed in the Fkh6−/− stomach, while immunohistochemical studies showed that comparable numbers of parietal cells were differentiated in both wild-type and Fkh6−/− stomachs. Ultrastructurally Fkh6−/− parietal cells were furnished with developed intracellular canaliculi and many mitochondria, but their canaluculi were not enlarged nor fully connected to the luminal surface even when animals were treated with histamine, suggesting that Fkh6−/− parietal cells were far less responsive to acid secretion-inducing stimulations. Some parietal cells contained secretory granules positively stained with anti-pepsinogen antibodies, indicating that they retained characteristics of oxynticopeptic cells found in lower vertebrates. We thus concluded that Fkh6 plays essential roles for the development and differentiation of parietal cells via epithelial-mesenchymal interactions.

Gastric physiology

The year has seen further evidence that Helicobacter pylori increases release of the acid-stimulating peptide gastrin and suppresses expression of the inhibitory hormone somatostatin in the gastric mucosa. Measurements of acid secretion have shown that H. pylori increases the duodenal acid load, but that under other circumstances the same bacterium decreases acid secretion. It is important to understand these different responses to H. pylori because they lead to different disease outcomes. While some are considering the effect of H. pylori on acid, others are exploring the effect of acid on H. pylori. The bacteria migrate from the antrum to the corpus of the stomach when acid secretion is suppressed with omeprazole.

Further applications of blood gas analysis to gastric acidity determination

It has been shown that the transient increase in total body bicarbonate that accompanies any acceleration of gastric acid secretion (the ‘alkaline tide’) is derivable from the associated changes in base excess in arterial blood and is precisely equivalent to the amount of acid secreted when the latter is simultaneously recovered. For the alkaline tide to qualify as a ‘tubeless’ measure of acid secretion, its equivalence to the latter has to be demonstrated without simultaneous aspiration of gastric juice. We therefore studied the course of the alkaline tide following pentagastrin injection and its relationship to pentagastrin-stimulated acid secretion as measured by aspiration on a separate occasion. In 12 duodenal ulcer patients, the sequential changes in base excess in arterial blood in response to pentagastrin invariably described coherent curves. Peak values occurred most frequently 45 min after injection. In 12 similar patients, alkaline tide 45 min after pentagastrin, as per analysis of arterialized venous blood, correlated well ( r = 0.86) with ‘peak acid output’ (PAO) as measured by aspiration at another time. In 14 patients post vagotomy and pyloroplasty for duodenal ulcer, the 45-min alkaline tide was determined as above and PAO was predicted from the previously established regression-line: The 3 patients with recurrent duodenal ulceration had the highest predicted values for PAO, clearly discriminating them from the others. Measurement of alkaline, tide holds promise as a valuable substitute for conventional gastric analysis. For the sake ???[MISSING PAGES] PAGE 10

Stimulation of inositol phosphate and diacylglycerol production by RHC 80267, a diacylglycerol-lipase inhibitor, in rat gastric parietal cells: effects on hydrogen ion secretion

RHC 80267, on inhibitor of diacylglycerol lipase, was used to investigate the role of diacylglycerol in acid secretion by isolated rat gastric parietal cells. Unexpectedly, RHC 80267 stimulated the production of inositol phosphates in [ 3H]inositol-prelabeled cells and increased levels of 32P-labeled phosphatidic acid to the same degree as did carbachol. RHC 80267 increased diacylglycerol to a greater extent than did carbachol, and additionally decreased levels of [ 3H]arachidonic acid. This suggests that RHC 80267 stimulated phospholipase C and inhibited diacylglycerol lipase in parietal cells. RHC inhibited [ 14C]aminopyrine uptake, a measure of acid secretion, stimulated by carbachol or by simultaneous addition of carbachol and dibutyryl-cAMP. These data support the model that the diacylglycerol/protein kinase C branch of the phosphoinositide system is inhibitory to acid secretion.

Histamine-mediated hyposmotic stimulation of gastric acid secretion.

Gastric glands incubated in hyposmotic medium (200 mOsm) accumulated aminopyrine, a measure of acid secretion, to the same extent as that of paired glands in isomotic medium containing histamine (10(-4) M). These maximal responses to hyposmolality and histamine were not additive. The hyposmotic response peaked earlier than the histamine response. Hyposmotic stimulation was nearly abolished by preincubation of the glands with metiamide and cimetidine, H-2 histamine antagonists. In the presence of histaminase, no hyposmotic stimulation occurred. The response to forskolin, a stimulant of adenylate cyclase, was equivalent in hyposmotic and isosmotic media. These results indicate that hyposmolality releases histamine from a paracrine cell in the gastric gland and that histamine binds to H-2 receptors on the parietal cell to initiate a cyclic AMP-mediated stimulation of acid secretion.

Prostaglandin E analogue inhibition of intrinsic factor release.

In many mammalian species (including humans) the parietal cell secretes both acid and intrinsic factor (IF). The aim of this study was to examine the direct effect of prostaglandin E analogues on basal and stimulated IF release in isolated, enriched rabbit parietal cells. The effects of graded concentrations (10(-12) to 10(-6) M) of 16,16-dimethyl prostaglandin E2 (DMPGE2) and 16-methyl,16-hydroxyl prostaglandin E1 (misoprostol) on submaximal histamine-stimulated (10(-6) M) secretion were tested. Both analogues failed to alter basal release of IF or aminopyrine accumulation (indirect measure of acid secretion). Increasing concentrations of DMPGE2 resulted in a dose-dependent inhibition of IF release (22 +/- 8% decrease at 10(-9) M; p less than 0.05) and a maximal effective response at 10(-7) M (54 +/- 9%; p less than 0.005). Dose-dependent inhibition of IF secretion was also observed with increasing concentrations of misoprostol, with a 22 +/- 7% decrease at 10(-9) M (p less than 0.05) and maximal effective inhibition at 10(-6) M (47 +/- 8%; p less than 0.01). Misoprostol and DMPGE2 inhibition of acid secretion paralleled IF release. Prostaglandin analogues appear to block IF release potently in histamine-stimulated parietal cells.

Functional and biochemical interaction of dibutyryl cyclic AMP with the phosphoinositide system in isolated rat parietal cells

The interaction of the muscarinic agonist carbachol and of dibutyryl cAMP on acid secretion and phosphoinositide second messenger metabolism were studied in rat gastric parietal cells. Compared to the added effects of each agonist alone aminopyrine uptake, a measure of acid secretion, was enhanced 2–4-fold by the combination of both compounds. In addition the ED50 for carbachol was left shifted in the presence of dibutyryl-cAMP. The cholinergic stimulation of inositol phosphate production was slightly inhibited by dibutyryl-cAMP while levels of diacylglycerol were not affected. Thus the interaction of the cAMP and the phosphoinositide systems involve potentiation and positive sensitivity modulation of the cholinergic response by cAMP which is mediated by events distal to the generation of phosphoinositide second messengers.

Muscarinic M2-receptors enhance polyphosphoinositol release in rat gastric mucosal cells

Muscarinic receptor types and their effects on the inositol phosphate second messenger system were studied in enzymatically dispersed rat gastric mucosal cells. Radioreeeptor binding studies indicated the presence of a single class of binding sites (4860 ± 875 sites cell ) and affinities of 0.42 ± 0.12 nM, 176 ± 32 nM and 13 μM for N-methylscopolamine, pirenzepine and carbachol, respectively. In cells prelabelled with myo-[ 3H]inositol carbachol induced a dose-dependent increase in inositol-1-phosphate in the presence of lithium with an ED 50 of 10 μM which was antagonized by atropine and pirenzepine (IC 50 9 and 700 nM, respectively). Carbachol stimulated amino[ 14C]pyrine uptake, used as a measure of acid secretion, with an ED 50 of 10 μM. The good correlation between these responses suggests a role for inositol phosphates in the muscarinic M2-receptor mediated acid secretion.

Inhibition of gastric acid secretion with a mast cell stabiliser, FPL-52694.

1 The effect on gastric acid secretion of a mast cell stabiliser FPL-52694 was examined in nine healthy volunteers. 2 The compound which is moderately well absorbed after oral ingestion, was taken for 5 days prior to the measurement of acid secretion and was also given intravenously during part of the gastric test. A submaximal dose of pentagastrin (0.3 microgram/kg/h) was given by intravenous infusion for 2 h in a controlled test and then after administration of FPL-52694. 3 There was a significant reduction (37%) in acid secretion during the second test which was probably due to the effect of the compound on mast cell degranulation in the gastric mucosa.

Further observations upon gastric function in rats after prolonged administration of an anticholinergic drug, propantheline bromide.

Gastric function was assessed in Wistar rats which received propantheline bromide by daily injection for 20 weeks. The results were compared with those from two control groups, one of which was injected daily with saline for 20 weeks. Gastric acid secretion, as measured by test meal and after ligation of the pylorus, was similar in all three groups. Acid secretion, as measured by test meal with pentagastrin 100 µg/kg body weight, gastric emptying, and fundic mucosal volume, expressed in terms of body weight, were all significantly increased in rats given propantheline. Only those measurements of acid secretion obtained by test meal with pentagastrin showed a significant correlation with fundic mucosal volume. Hence, since this method provides the most accurate indication of secretory capacity, it is concluded that the prolonged parenteral administration of propantheline may lead to an increase in parietal cell mass and its correlate, maximal secretory capacity. The mechanism by which these changes are produced is obscure.

Continuous recording of acid gastric secretion in the rat.

A method is described for the continuous recording of acid gastric secretion in the rat. The stomach of the rat anaesthetized with urethane is perfused with a dilute sodium hydroxide solution by way of the oesophagus and the pH of the fluid emerging from a cannula in the pylorus is registered graphically. In passing through the stomach, the perfusate collects sufficient buffer to act as an approximately linear buffer system over the relevant range, so that the change in pH becomes a measure of acid secretion. The preparation is suitable for the bioassay of secretory stimulants. Ten or more drug doses can be administered in succession in one preparation, so that each animal serves as a self-contained assay unit. Intravenous doses of histamine, methacholine, carbachol and acetylcholine produce a graded and reversible stimulation of acid secretion. The secretory effect of histamine is markedly and specifically potentiated by antihistaminases.