Unique roles of G protein-coupled histamine H 2 and gastrin receptors in growth and differentiation of gastric mucosa

Yasushi Fukushima, Toshimitsu Matsui, Toshihito Saitoh, Masao Ichinose, Keisuke Tateishi, Takayuki Shindo, Midori Fujishiro, Hideyuki Sakoda, Nobuhiro Shojima, Akifumi Kushiyama, Satoru Fukuda, Motonobu Anai, Hiraku Ono, Masashi Oka, Yasuhito Shimizu, Hiroki Kurihara, Ryozo Nagai, Takashi Ishikawa, Tomoichiro Asano, Masao Omata

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Disruption of histamine H 2 receptor and gastrin receptor had different effects growth of gastric mucosa: hypertrophy and atrophy, respectively. To clarify the roles of gastrin and histamine H 2 receptors in gastric mucosa, mice deficient in both (double-null mice) were generated and analyzed. Double-null mice exhibited atrophy of gastric mucosae, marked hypergastrinemia and higher gastric pH than gastrin receptor-null mice, which were unresponsive even to carbachol. Comparison of gastric mucosae from 10-week-old wild-type, histamine H 2 receptor-null, gastrin receptor-null and double-null mice revealed unique roles of these receptors in gastric mucosal homeostasis. While small parietal cells and increases in the number and mucin contents of mucous neck cells were secondary to impaired acid production, the histamine H 2 receptor was responsible for chief cell maturation in terms of pepsinogen expression and type III mucin. In double-null and gastrin receptor-null mice, despite gastric mucosal atrophy, surface mucous cells were significantly increased, in contrast to gastrin-null mice. Thus, it is conceivable that gastrin-gene product(s) other than gastrin-17, in the stimulated state, may exert proliferative actions on surface mucous cells independently of the histamine H 2 receptor. These findings provide evidence that different G-protein coupled-receptors affect differentiation into different cell lineages derived from common stem cells in gastric mucosa.

Original languageEnglish
Pages (from-to)243-252
Number of pages10
JournalEuropean Journal of Pharmacology
Issue number3
StatePublished - 19 Oct 2004
Externally publishedYes


  • Double-null
  • G protein
  • Histamine H
  • mouse


Dive into the research topics of 'Unique roles of G protein-coupled histamine H 2 and gastrin receptors in growth and differentiation of gastric mucosa'. Together they form a unique fingerprint.

Cite this