scholarly journals Transcriptional profiling of gastrin-regulated genes in mouse stomach

2007 ◽  
Vol 29 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Renu N. Jain ◽  
Linda C. Samuelson
Keyword(s):  
Acid Secretion ◽  
Gastric Acid ◽  
Parietal Cell ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Polymerase Chain Reaction Analysis ◽  
Ecl Cell ◽  
Severe Impairment ◽  
Basal Acid ◽  
Acid Secreting

Gastrin, a potent stimulator of gastric acid secretion, primarily targets the acid-secreting parietal cells and histamine-secreting enterochromaffin-like (ECL) cells in the stomach. Accordingly, gastrin-deficient (GAS-KO) mice have a severe impairment in acid secretion. The aim of this study was to characterize changes in gene expression in GAS-KO mice to identify gastrin-regulated genes and to gain insight into how gastric cell types are regulated by gastrin and acid secretion. Affymetrix microarray analysis of GAS-KO and wild-type mice identified numerous differentially expressed transcripts. The results were compared with GAS-KO mice treated with gastrin to identify genes that were gastrin responsive. Finally, genes that were primarily changed due to gastrin and not hypochlorhydria were identified by comparison to mice that are deficient in both gastrin and cholecystokinin (GAS/CCK-KO), since these mice have restored basal acid secretion. The data were validated by quantitative reverse transcriptase polymerase chain reaction analysis. Interestingly, a number of inflammatory response genes were induced in GAS-KO mice and normalized in GAS/CCK-KO mice, suggesting that they were increased in response to low gastric acid. Moreover, a number of parietal cell transcripts that were downregulated in GAS-KO mice were similarly restored in GAS/CCK-KO mice, suggesting that parietal cell changes were also primarily associated with hypochlorhydria. In contrast, ECL cell genes that were markedly downregulated in GAS-KO mice continued to be reduced in GAS/CCK-KO mice, demonstrating that gastrin coordinately regulates a number of ECL cell genes, including several involved in histamine synthesis and secretion.

Sa1346 HYPERGASTRINEMIA DUE TO P-CAB (AN EXTREMELY POTENT GASTRIC ACID SECRETION SUPPRESSOR) USE CAUSE SEVERELY PARIETAL CELL PROTRUSION AND ECL CELL HYPERPLASIA.

2020 ◽  
Vol 158 (6) ◽  
pp. S-325
Author(s):  
Takuji Yamasaki ◽  
Yoshihiro Akita ◽  
Haruna Miyashita ◽  
Ryosuke Miyazaki ◽  
Yuki Maruyama ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Parietal Cell ◽  
Cell Hyperplasia ◽  
Cell Protrusion ◽  
Ecl Cell

scholarly journals Metabolism and gastric acid secretion. Substrate-dependency of aminopyrine accumulation in isolated rat parietal cells

1985 ◽  
Vol 227 (1) ◽  
pp. 223-229 ◽  
Author(s):  
G P Shaw ◽  
N G Anderson ◽  
P J Hanson
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Parietal Cell ◽  
Parietal Cells ◽  
Intestinal Epithelial ◽  
Acid Secreting ◽  
High Concentrations ◽  
Isolated Rat

The substrate-dependency of gastric acid secretion was investigated in isolated rat parietal cells by using the accumulation of the weak base aminopyrine as an index of acid secretion. Exogenous substrates enhanced accumulation of aminopyrine in rat parietal cells stimulated by secretagogues, and this effect was probably directly related to the provision of energy for acid secretion. At physiological concentrations, certain of the substrates (glucose, oleate, lactate, D-3-hydroxybutyrate, L-isoleucine, L-valine and acetoacetate) could support acid secretion, with glucose being the most effective. L-Leucine and acetate were only effective stimulators of parietal-cell aminopyrine accumulation at high concentrations (5mM). L-Glutamine was unable to stimulate aminopyrine accumulation even at high concentrations, and glutaminase activity in parietal cells was estimated to be low by comparison with small-intestinal epithelial cells. Variation in the concentrations of D-3-hydroxybutyrate and L-isoleucine, but not of glucose, within the physiological range affected their ability to support aminopyrine accumulation. The presence of 5 mM-L-isoleucine, 5 mM-lactate and combinations of certain substrates at physiological concentrations produced aminopyrine accumulation in stimulated parietal cells that was greater than that obtained in cells incubated with 5 mM-glucose alone. In conclusion, fulfillment of the metabolic requirements of the acid-secreting parietal cell under physiological circumstances requires a combination of substrates, and integration of the results with previous data [Anderson & Hanson (1983) Biochem. J. 210, 451-455; 212, 875-879] suggests that after overnight starvation in vivo metabolism of glucose, D-3-hydroxybutyrate and L-isoleucine may be of particular importance.

scholarly journals CORRELATION OF THE FINE STRUCTURE OF THE GASTRIC PARIETAL CELL (DOG) WITH FUNCTIONAL ACTIVITY OF THE STOMACH

1961 ◽  
Vol 11 (2) ◽  
pp. 349-363 ◽  
Author(s):  
A. W. Sedar ◽  
M. H. F. Friedman
Keyword(s):  
Fine Structure ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Parietal Cell ◽  
Parietal Cells ◽  
Gastric Glands ◽  
Secretory Cycle ◽  
Thin Sections ◽  
Acid Secreting

The fine structure of the parietal (oxyntic) cell in the gastric glands (corpus of the stomach) of the dog was examined under conditions of active gastric acid secretion and compared with cellular structure in the non-acid-secretory (basal) state. Animals, in both acute and chronic experiments, were equipped with gastric fistulae so that gastric juice could be collected for analysis of total acidity, free acidity, volume, and pH prior to biopsy of the gastric mucosa. The specimens of mucosa were fixed in buffered OsO4 and embedded in n-butyl methacrylate and the thin sections were stained with lead hydroxide before examination in the electron microscope. A majority of parietal cells showed an alteration of fine structure during stimulation of gastric acid secretion by a number of different techniques (electrical vagal stimulation, histamine administration, or insulin injection). The changes in fine structure affected mainly the smooth surfaced vesicular elements and the intracellular canaliculi in the cytoplasm of the cell. The mitochondria also appeared to be involved to some extent. During acid secretion a greater concentration of smooth surface profiles is found adjacent to the walls of the intracellular canaliculi; other parietal cells exhibited a marked decrease in number of smooth surfaced elements. Intracellular canaliculi, always present in non-acid-secreting oxyntic cells, develop more extensively in cells of acid-secreting gastric glands. The surface area of these canaliculi is greatly increased by the elaboration of a large number of closely approximated and elongated microvilli. Still other parietal cells apparently in a different stage of the secretory cycle exhibit non-patent canaliculi lacking prominence; such cells have very few smooth surfaced vesicular elements. These morphological findings correlated with the acid-secretory state of the stomach provide evidence that the parietal cell participates in the process of acid secretion.

scholarly journals Gene expression profiling of gastrin target genes in parietal cells

2006 ◽  
Vol 24 (2) ◽  
pp. 124-132 ◽  
Author(s):  
Renu N. Jain ◽  
Cynthia S. Brunkan ◽  
Catherine S. Chew ◽  
Linda C. Samuelson
Keyword(s):  
Gene Expression ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Parietal Cell ◽  
Target Genes ◽  
Adaptor Protein ◽  
Parietal Cells ◽  
Cell Gene Expression ◽  
Cell Gene

Previous studies demonstrated that mice with a null mutation in the gene encoding the hormone gastrin have impaired gastric acid secretion. Hence, the aim of this study was to evaluate changes in the acid-secreting parietal cell in gastrin-deficient (GAS-KO) mice. Analysis of several transcripts encoding parietal cell proteins involved in gastric acid secretion showed reduced abundance in the GAS-KO stomach, including H+,K+-ATPase α- and β-subunits, KCNQ1 potassium channel, aquaporin-4 water channel, and creatine kinase B, which were reversed by gastrin infusion for 1 wk. Although mRNA and protein levels of LIM and SH3 domain-containing protein-1 (LASP-1) were not greatly changed in the mutant, there was a marked reduction in phosphorylation, consistent with its proposed role as a cAMP signal adaptor protein associated with acid secretion. A more comprehensive analysis of parietal cell gene expression in GAS-KO mice was performed using the Affymetrix U74AV2 chip with RNA from parietal cells purified by flow cytometry to >90%. Comparison of gene expression in GAS-KO and wild-type mice identified 47 transcripts that differed by greater than or equal to twofold, suggesting that gastrin affects parietal cell gene expression in a specific manner. The differentially expressed genes included several genes in signaling pathways, with a substantial number (20%) known to be target genes for Wnt and Myc.

Gastric acid secretion and parietal cell mass: effects of thyroidectomy and thyroxine

1989 ◽  
Vol 256 (6) ◽  
pp. G975-G978 ◽  
Author(s):  
K. O. Adeniyi ◽  
M. O. Olowookorun
Keyword(s):  
Gastric Mucosa ◽  
Thyroid Hormones ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Parietal Cell ◽  
Cell Function ◽  
Cell Mass ◽  
Chronic Administration ◽  
Basal Acid

The role of thyroid hormones on parietal cell function and number was studied in the rat. Chronic administration of thyroxine (6-8 micrograms/100 g body wt/day) for 35 days significantly increased parietal cell mass (from 21.18 +/- 0.13 x 10(6) to 26.71 +/- 0.14 x 10(6] as well as basal acid secretion (from 3.69 +/- 0.08 to 4.99 +/- 0.16 mueq/10 min) and histamine-stimulated acid secretion (from 2.45 +/- 0.12 to 3.69 +/- 0.21 mueq/10 min). Thyroidectomy decreased the number of parietal cells in the gastric mucosa (to 10.48 +/- 0.09 x 10(6] and basal acid secretion (to 3.09 +/- 0.08 mueq/10 min). Histamine (0.2 mg) injection into the thyroidectomized rats increased acid secretion by only 1.41 +/- 0.06 mueq/10 min as against 2.45 +/- 0.12 mueq/10 min obtained for control rats. The results suggest that thyroid hormones regulate basal and secretagogue-stimulated acid secretion via their effects on parietal cell mass.

III. Lessons learned from gastrin gene deletion in mice

1999 ◽  
Vol 277 (3) ◽  
pp. G500-G505 ◽  
Author(s):  
Karen L. Hinkle ◽  
Linda C. Samuelson
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Gene Deletion ◽  
Embryonic Stem ◽  
Lessons Learned ◽  
Mouse Mutants ◽  
Functional Maturation ◽  
Ecl Cell ◽  
Secretory System

Gastrin is the principal hormonal inducer of gastric acid secretion. Chronic hypergastrinemia, leading to hypersecretion of gastric acid and increased proliferation of parietal and enterochromaffin-like (ECL) cells, has been well described. In contrast, the physiological consequences of chronic gastrin deficiency had been poorly understood until the recent genetic engineering of mouse mutants containing a gastrin gene deletion by homologous recombination in embryonic stem cells. This themes article describes the consequences of constitutive gastrin deficiency on the development and physiology of the stomach. A lack of gastrin disrupts basal gastric acid secretion and renders the acid secretory system unresponsive to acute histaminergic, cholinergic, and gastrinergic stimulation. The defect in acid secretion is greater than would have been predicted from previous studies in which gastrin action was acutely blocked. Cellular changes include thinning of the gastric mucosa in the gastrin-deficient mice, with a reduction in parietal cells and reduced expression of markers of parietal and ECL cell-differentiated functions. The results suggest that gastrin is required for the functional maturation of the acid-secretory system.

PACAP stimulates gastric acid secretion in the rat by inducing histamine release

2001 ◽  
Vol 281 (4) ◽  
pp. G997-G1003 ◽  
Author(s):  
Arne K. Sandvik ◽  
Guanglin Cui ◽  
Ingunn Bakke ◽  
Bjørn Munkvold ◽  
Helge L. Waldum
Keyword(s):  
Acid Secretion ◽  
Histamine Release ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Rat Stomach ◽  
Neurohumoral Regulation ◽  
Ecl Cell ◽  
Pituitary Adenylate Cyclase ◽  
Awake Rat

Previous studies have shown that pituitary adenylate cyclase-activating peptide (PACAP) stimulates enterochromaffin-like (ECL) cell histamine release, but its role in the regulation of gastric acid secretion is disputed. This work examines the effect of PACAP-38 on aminopyrine uptake in enriched rat parietal cells and on histamine release and acid secretion in the isolated vascularly perfused rat stomach and the role of PACAP in vagally (2-deoxyglucose) stimulated acid secretion in the awake rat. PACAP has no direct effect on the isolated parietal cell as assessed by aminopyrine uptake. PACAP induces a concentration-dependent histamine release and acid secretion in the isolated stomach, and its effect on histamine release is additive to gastrin. The histamine H2antagonist ranitidine potently inhibits PACAP-stimulated acid secretion without affecting histamine release. Vagally stimulated acid secretion is partially inhibited by a PACAP antagonist. The results from the present study strongly suggest that PACAP plays an important role in the neurohumoral regulation of gastric acid secretion. Its effect seems to be mediated by the release of ECL cell histamine.

Gastric Enterochromaffin-Like Cells and the Regulation of Acid Secretion

Physiology ◽  
1996 ◽  
Vol 11 (2) ◽  
pp. 57-62
Author(s):  
G Sachs ◽  
C Prinz
Keyword(s):  
Cell Growth ◽  
Acid Secretion ◽  
Histamine Release ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Histidine Decarboxylase ◽  
Major Pathway ◽  
Ecl Cell

The interaction of gastrin, somatostatin, and other transmitters at the level of the histamine-containing enterochromaffin (ECL) cell is the major pathway determining rate of gastric acid secretion. Gastrin stimulates ECL cell elevation of [Ca2+]i, synthesis of histidine decarboxylase, histamine release, and cell growth by binding at a cholecystokinin-B receptor. Somatostatin inhibits gastrin-dependent elevation of [Ca2+]i and hence histamine release by binding to stomatostatin receptor 2 subtype.

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