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

Susumu Okabe, Kazuharu Furutani, Kazuhiko Maeda, Takeshi Aihara, Teruaki Fujishita, Shunsuke Tonai

Research output: Contribution to journalReview article

2 Scopus citations

Abstract

Mechanisms for gastric acid secretion have been elucidated through invention of new methods and new drugs. Current genetic technology have generated knockout (KO) mice lacking receptors such as CCK2, histamine H2, muscarinic M3 and M1, or enzymes such as histidine decarboxylase (HDC) and H+,K+-ATPase. Here, we review the functional and morphological changes in the gastric mucosa of such KO mice. In M3R-KO mice (intragastric pH 5.9), carbachol, histamine and gastrin stimulated acid secretion like they did in wild-type mice. Carbachol-stimulated acid secretion was significantly inhibited by famotidine and pirenzepine. The serum gastrin level in M3R-KO mice was increased, yet the stomach weight and the gastric mucosa remained unchanged. In H2R-KO mice (intragastric pH 3.0), serum gastrin and mucosal histamine levels significantly increased. Carbachol significantly stimulated acid secretion, yet histamine and gastrin had little or no effect on acid secretion. The stomach wet weight increased with time after birth and the serum albumin level was decreased. In the gastric mucosa with hyperplasia, numerous enlarged cysts and a marked expression of TGF-α were observed, indicating the occurrence of Menetrier's disease like mucosal changes. G/D cell ratio was greatly increased, providing evidence of the increased serum gastrin level. In HDC-KO mice (intragastric pH 4.5), the stomach weight was also increased 6 mo after birth, with no enlarged cysts in the gastric mucosa. Conclusion: The above results indicate that KO mice can be used to yield many important findings that selective antagonists cannot reveal.

Original languageEnglish (US)
Pages (from-to)159-171
Number of pages13
JournalFolia Pharmacologica Japonica
Volume120
Issue number3
DOIs
StatePublished - Sep 18 2002
Externally publishedYes

Keywords

  • CCKR-KO
  • HR-KO
  • HDC-KO
  • Knockout mice
  • MR-KO

ASJC Scopus subject areas

  • Pharmacology

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