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

Gastroenterology ◽

10.1053/gast.2002.30312 ◽

2002 ◽

Vol 122 (1) ◽

pp. 145-155 ◽

Cited By ~ 65

Author(s):

Satoshi Tanaka ◽

Kiyomi Hamada ◽

Noboru Yamada ◽

Yuko Sugita ◽

Shunsuke Tonai ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Histidine Decarboxylase ◽

Deficient Mice

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Regulatory mechanism of gastric acid secretion and mucosal integrity. An analysis with various gene deficient mice.

Folia Pharmacologica Japonica ◽

10.1254/fpj.120.159 ◽

2002 ◽

Vol 120 (3) ◽

pp. 159-171 ◽

Cited By ~ 2

Author(s):

Susumu OKABE ◽

Kazuharu FURUTANI ◽

Kazuhiko MAEDA ◽

Takeshi AIHARA ◽

Teruaki FUJISHITA ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Regulatory Mechanism ◽

Mucosal Integrity ◽

Deficient Mice

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Gastric Enterochromaffin-Like Cells and the Regulation of Acid Secretion

Physiology ◽

10.1152/physiologyonline.1996.11.2.57 ◽

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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Gastric acid secretion in cyclooxygenase-1 deficient mice

Alimentary Pharmacology & Therapeutics ◽

10.1046/j.1365-2036.2000.00836.x ◽

2000 ◽

Vol 14 (10) ◽

pp. 1365-1370 ◽

Cited By ~ 6

Author(s):

F. Borrelli ◽

N. J. Welsh ◽

G. Sigthorsson ◽

R. Simpson ◽

A. Palizban ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Cyclooxygenase 1 ◽

Deficient Mice

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Impaired gastric acid secretion in mast cell-deficient mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.1.g41 ◽

1990 ◽

Vol 259 (1) ◽

pp. G41-G47 ◽

Cited By ~ 2

Author(s):

D. J. Stechschulte ◽

D. C. Morris ◽

R. L. Jilka ◽

D. J. Stechschulte ◽

K. N. Dileepan

Keyword(s):

Mast Cell ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Parietal Cells ◽

Secretory Response ◽

H2 Antagonist ◽

Significant Difference ◽

Basal Acid ◽

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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