Gastric acid secretion in cyclooxygenase-1 deficient mice

Gastric acid secretion in normal (+/+) C57B1/6J mice and congeneic, mast cell-deficient (mi/mi) C57B1/6J mice was examined. The mast cell-deficient animals had approximately 50% of the normal quantity of gastric histamine and a blunted basal acid level and secretory response. These observations were noted despite the presence of parietal cells, which were normal in number and morphology. The H2-antagonist ranitidine inhibited basal acid secretion in both groups of animals. Exogenous histamine induced a significant secretory response in normal and mast cell-deficient groups, but only the secretory response in normal animals could be blocked by the H2-antagonist. Treatment of mast cell-deficient animals with histamine for seven consecutive days before stimulation did not restore the histamine response to the normal (+/+) levels. The normal animals demonstrated an acid secretory response to pentagastrin. Mast cell-deficient mice also responded to pentagastrin, but the response was less than that observed in the normal animals, and a significant difference was not evident in all experiments. Furthermore, simultaneous injection of mast cell-deficient animals with histamine and pentagastrin did not restore pentagastrin responsiveness to normal levels, although the histamine concentration used was sufficient to raise acid secretion to basal levels of normal mice. These results support the conclusion that non-mast cell histamine only partially contributes to basal gastric acid secretion and is insufficient to facilitate full parietal cell responsiveness. Furthermore, pentagastrin requires the presence of mast cells to elicit a maximal secretory response but can use non-mast cell histamine to activate the parietal cells for acid secretion.

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Effects of Cyclooxygenase-1 and -2 Inhibition on Gastric Acid Secretion and Cardiovascular Functions in Rats

Pharmacology ◽

10.1159/000089834 ◽

2006 ◽

Vol 76 (2) ◽

pp. 84-92 ◽

Cited By ~ 6

Author(s):

Maristella Adami ◽

Gabriella Coppelli ◽

Elena Guaita ◽

Cristina Pozzoli ◽

Alessandro Menozzi ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Cyclooxygenase 1 ◽

Cardiovascular Functions

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Impaired gastric acid secretion in gastrin-deficient mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.274.3.g561 ◽

1998 ◽

Vol 274 (3) ◽

pp. G561-G568 ◽

Cited By ~ 50

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.

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ECL cells and gastric acid secretion in gastrin-deficient mice

Gastroenterology ◽

10.1016/s0016-5085(98)84616-7 ◽

1998 ◽

Vol 114 ◽

pp. A1135

Author(s):

D Chen ◽

T Koh ◽

C-M Zhao ◽

R Håkanson ◽

TC Wang

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Ecl Cells ◽

Deficient Mice

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Enhancement of gastric acid secretion by histamine in histidine decarboxylase-deficient mice

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)47604-x ◽

2000 ◽

Vol 82 ◽

pp. 31

Author(s):

Satoshi Tanaka ◽

Satoru Takahashi ◽

Hiroshi Ohtsu ◽

Takehiko Watanabe ◽

Susumu Okabe ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Histidine Decarboxylase ◽

Deficient Mice

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I. Physiological studies with gastrin in transgenic mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.277.1.g6 ◽

1999 ◽

Vol 277 (1) ◽

pp. G6-G11 ◽

Cited By ~ 13

Author(s):

Timothy C. Wang ◽

Graham J. Dockray

Keyword(s):

Transgenic Mice ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Parietal Cell ◽

Knockout Mice ◽

Recent Progress ◽

Cell Function ◽

Deficient Mice

The role of gastrin in the regulation of gastrointestinal growth and acid secretion has been addressed through recent studies involving transgenic and knockout mice. The role of gastrin as a key modulator of parietal cell function and gastric acid secretion has been confirmed through studies in mice deficient in either gastrin or the gastrin/CCK-B receptor. However, although gastrin-deficient mice show no changes in gastric proliferation, they do show reduced colonic proliferation, and rates of colonic proliferation are increased in transgenic mice overexpressing glycine-extended gastrin or progastrin. This themes article highlights recent progress in our understanding of the biology of gastrin through studies in genetically modified mice.

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Impairment of gastric acid secretion and increase of embryonic lethality in Foxq1-deficient mice

Cytogenetic and Genome Research ◽

10.1159/000125833 ◽

2008 ◽

Vol 121 (2) ◽

pp. 88-95 ◽

Cited By ~ 15

Author(s):

W. Goering ◽

I.M. Adham ◽

B. Pasche ◽

J. Männer ◽

M. Ochs ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Embryonic Lethality ◽

Deficient Mice

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Role of cyclooxygenase-2 in modulating gastric acid secretion in the normal and inflamed rat stomach

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.279.6.g1292 ◽

2000 ◽

Vol 279 (6) ◽

pp. G1292-G1297 ◽

Cited By ~ 27

Author(s):

Kirsty Barnett ◽

Cameron J. Bell ◽

Webb McKnight ◽

Michael Dicay ◽

Keith A. Sharkey ◽

...

Keyword(s):

Gastric Ulcer ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Ulcer Healing ◽

Cyclooxygenase 2 ◽

Gastric Ulcer Healing ◽

Cyclooxygenase 1 ◽

Basal Acid ◽

Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs elevate gastric acid secretion, possibly contributing to their ability to interfere with gastric ulcer healing. Inhibitors of cyclooxygenase-2 have been shown to delay experimental gastric ulcer healing. In the present study, we tested the hypothesis that cyclooxygenase-2-derived prostaglandins modulate gastric acid secretion. Studies were performed in normal rats and in rats with iodoacetamide-induced gastritis. Inflammation in the latter group was confirmed histologically and by a threefold increase in tissue levels of the granulocyte marker myeloperoxidase and was also associated with overexpression of cyclooxygenase-2 in the stomach. Basal acid secretion in both groups of rats was not affected by pretreatment with DuP-697, a selective inhibitor of cyclooxygenase-2. A nonselective cyclooxygenase inhibitor, indomethacin, had no effect on acid secretion in normal rats but caused a doubling of acid secretion in the rats with gastritis. DuP-697 had no effect on pentagastrin-induced secretion in either group of rats. Gastritis itself was associated with significantly increased pentagastrin-induced acid secretion, and this was further increased in rats pretreated with indomethacin. These results suggest that in a setting of gastric inflammation, prostaglandins derived from cyclooxygenase-1, not cyclooxygenase-2, exert inhibitory effects on acid secretion.

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