scholarly journals The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands

2005 ◽  
Vol 289 (6) ◽  
pp. G1084-G1090 ◽  
Author(s):  
Matthias M. Dufner ◽  
Philipp Kirchhoff ◽  
Christine Remy ◽  
Patricia Hafner ◽  
Markus K. Müller ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Divalent Cations ◽  
Parietal Cells ◽  
Trivalent Cation ◽  
Calcium Sensing Receptor ◽  
Gastric Glands ◽  
Calcium Sensing

Gastric acid secretion is activated by two distinct pathways: a neuronal pathway via the vagus nerve and release of acetylcholine and an endocrine pathway involving gastrin and histamine. Recently, we demonstrated that activation of H+-K+-ATPase activity in parietal cells in freshly isolated rat gastric glands is modulated by the calcium-sensing receptor (CaSR). Here, we investigated if the CaSR is functionally expressed in freshly isolated gastric glands from human patients undergoing surgery and if the CaSR is influencing histamine-induced activation of H+-K+-ATPase activity. In tissue samples obtained from patients, immunohistochemistry demonstrated the expression in parietal cells of both subunits of gastric H+-K+-ATPase and the CaSR. Functional experiments using the pH-sensitive dye 2′,7′-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein and measurement of intracellular pH changes allowed us to estimate the activity of H+-K+-ATPase in single freshly isolated human gastric glands. Under control conditions, H+-K+-ATPase activity was stimulated by histamine (100 μM) and inhibited by omeprazole (100 μM). Reduction of the extracellular divalent cation concentration (0 Mg2+, 100 μM Ca2+) inactivated the CaSR and reduced histamine-induced activation of H+-K+-ATPase activity. In contrast, activation of the CaSR with the trivalent cation Gd3+ caused activation of omeprazole-sensitive H+-K+-ATPase activity even in the absence of histamine and under conditions of low extracellular divalent cations. This stimulation was not due to release of histamine from neighbouring enterochromaffin-like cells as the stimulation persisted in the presence of the H2 receptor antagonist cimetidine (100 μM). Furthermore, intracellular calcium measurements with fura-2 and fluo-4 showed that activation of the CaSR by Gd3+ led to a sustained increase in intracellular Ca2+ even under conditions of low extracellular divalent cations. These experiments demonstrate the presence of a functional CaSR in the human stomach and show that this receptor may modulate the activity of acid-secreting H+-K+-ATPase in parietal cells. Furthermore, our results show the viability of freshly isolated human gastric glands and may allow the use of this preparation for experiments investigating the physiological regulation and properties of human gastric glands in vitro.

l-Type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells

2005 ◽  
Vol 289 (4) ◽  
pp. G664-G669 ◽  
Author(s):  
Stephanie M. Busque ◽  
Jane E. Kerstetter ◽  
John P. Geibel ◽  
Karl Insogna
Keyword(s):  
Amino Acids ◽  
Atpase Activity ◽  
Acid Secretion ◽  
Ex Vivo ◽  
Parietal Cells ◽  
Secretory Cells ◽  
Calcium Sensing Receptor ◽  
Gastric Glands ◽  
Calcium Sensing ◽  
System L

Parietal cells are the primary acid secretory cells of the stomach. We have previously shown that activation of the calcium-sensing receptor (CaSR) by divalent (Ca2+) or trivalent (Gd3+) ions stimulates acid production in the absence of secretagogues by increasing H+,K+-ATPase activity. When overexpressed in HEK-293 cells, the CaSR can be allosterically activated by l-amino acids in the presence of physiological concentrations of extracellular Ca2+ (Cao2+; 1.5–2.5 mM). To determine whether the endogenously expressed parietal cell CaSR is allosterically activated by l-amino acids, we examined the effect of the amino acids l-phenylalanine (l-Phe), l-tryptophan, and l-leucine on acid secretion. In ex vivo whole stomach preparations, exposure to l-Phe resulted in gastric luminal pH significantly lower than controls. Studies using d-Phe (inactive isomer) failed to elicit a response on gastric pH. H+-K+-ATPase activity was monitored by measuring the intracellular pH (pHi) of individual parietal cells in isolated rat gastric glands and calculating the rate of H+ extrusion. We demonstrated that increasing Cao2+ in the absence of secretagogues caused a dose-dependent increase in H+ extrusion. These effects were amplified by the addition of amino acids at various Cao2+ concentrations. Blocking the histamine-2 receptor with cimetidine or inhibiting system l-amino acid transport with 2-amino-2-norbornane-carboxylic acid did not affect the rate of H+ extrusion in the presence of l-Phe. These data support the conclusion that amino acids, in conjunction with a physiological Cao2+ concentration, can induce acid secretion independent of hormonal stimulation via allosteric activation of the stomach CaSR.

Impaired gastric acid secretion in gastrin-deficient mice

1998 ◽  
Vol 274 (3) ◽  
pp. G561-G568 ◽  
Author(s):  
Lennart Friis-Hansen ◽  
Frank Sundler ◽  
Ying Li ◽  
Patrick J. Gillespie ◽  
Thomas L. Saunders ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Histidine Decarboxylase ◽  
Embryonic Stem ◽  
Parietal Cells ◽  
Gastric Glands ◽  
Partial Restoration ◽  
Ecl Cells ◽  
Deficient Mice

To further understand the role of the peptide hormone gastrin in the development and function of the stomach, we have generated gastrin-deficient mice by gene targeting in embryonic stem cells. Mutant mice were viable and fertile, without obvious visible abnormalities. However, gastric function was severely affected by the loss of gastrin. Basal gastric acid secretion was abolished and could not be induced by histamine, carbachol, or gastrin. Histological analysis revealed alterations in the two cell types primarily involved in acid secretion, parietal and enterochromaffin-like (ECL) cells. Parietal cells were reduced in number with an accumulation of immature cells lacking H+-K+-adenosinetriphosphatase (H+-K+-ATPase). ECL cells were positioned closer to the base of the gastric glands, with markedly lower expression of histidine decarboxylase. Gastrin administration for 6 days reversed the effects of the gastrin deficiency, leading to an increase in the number of mature, H+-K+-ATPase-positive parietal cells and a partial restoration of acid secretion. The results show that gastrin is critically important for the function of the acid secretory system.

Tu1899 Gastric Acid Secretion via the H+-ATPase Is Modulated by the Calcium-Sensing Receptor

2015 ◽  
Vol 148 (4) ◽  
pp. S-931
Author(s):  
Tariq I. Alfadda ◽  
Abrar M. Alsaihati ◽  
Anne J. Schmitt ◽  
Katja Bloecker ◽  
Sascha Kopic ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

QS90. Calcium-Sensing Receptor: A Potential Off-Switch for Gastric Acid Secretion

2009 ◽  
Vol 151 (2) ◽  
pp. 286
Author(s):  
E. Arena ◽  
U. Hellmich ◽  
A. Schilcher ◽  
J.P. Geibel
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

scholarly journals Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach

2008 ◽  
Vol 105 (46) ◽  
pp. 17955-17960 ◽  
Author(s):  
Jie Xu ◽  
Penghong Song ◽  
Marian L. Miller ◽  
Frank Borgese ◽  
Sharon Barone ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Cultured Cells ◽  
Normal Growth ◽  
Chloride Secretion ◽  
Parietal Cells ◽  
Gastric Glands ◽  
Anion Transporter ◽  
Immunofluorescence Labeling

Slc26a9 is a recently identified anion transporter that is abundantly expressed in gastric epithelial cells. To study its role in stomach physiology, gene targeting was used to prepare mice lacking Slc26a9. Homozygous mutant (Slc26a9−/−) mice appeared healthy and displayed normal growth. Slc26a9 deletion resulted in the loss of gastric acid secretion and a moderate reduction in the number of parietal cells in mutant mice at 5 weeks of age. Immunofluorescence labeling detected the H-K-ATPase exclusively on the apical pole of gastric parietal cells in Slc26a9−/− mice, in contrast to the predominant cytoplasmic localization in Slc26a9+/+ mice. Light microscopy indicated that gastric glands were dilated, and electron micrographs displayed a distinct and striking absence of tubulovesicles in parietal cells and reductions in the numbers of parietal and zymogen cells in Slc26a9−/− stomach. Expression studies indicated that Slc26a9 can function as a chloride conductive pathway in oocytes as well as a Cl−/HCO3− exchanger in cultured cells, and localization studies in parietal cells detected its presence in tubulovesicles. We propose that Slc26a9 plays an essential role in gastric acid secretion via effects on the viability of tubulovesicles/secretory canaliculi and by regulating chloride secretion in parietal cells.

M1685 Role of Calcium-Sensing Receptor (CaSR) on Gastric Acid Secretion in Isolated Mouse Stomachs

2010 ◽  
Vol 138 (5) ◽  
pp. S-398
Author(s):  
Masafumi Koyama ◽  
Shusaku Hayashi ◽  
Eitaro Aihara ◽  
Shinichi Kato ◽  
Koji Takeuchi
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

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.

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