Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor–deficient mice

The present study clearly demonstrates that H2 receptor -mediated signal(s) are required for cellular homeostasis of the gastric mucosa and normally formed secretory membranes in parietal cells

Takashi Kobayashi; Shunsuke Tonai; Yasunobu Ishihara; Ritsuko Koga; Susumu Okabe; Takeshi Watanabe

2008

Scholarcy highlights

  • The oxyntic mucosa is composed of numerous blind tubular units containing various cell types
  • In the present study, we clarified the physiological roles of H2 receptor-mediated signals in the gastric mucosa by using H2R-deficient mice
  • The H2R null mutant mice exhibited rather unexpectedly normal basal gastric pH, which is clearly distinct from the elevated gastric pH observed in conventional mice treated with H2R antagonists
  • The M1R antagonist, telenzepine, could inhibit acid secretion, and carbachol normally induced acid secretion in H2R–/– mice. These results indicate that impairment of acid secretion due to the absence of H2R could be overcome by cholinergic signaling
  • This phenomenon leads us to speculate that chronic application of H2R antagonists may reduce their efficacy as inhibitors of acid secretion due to compensation with signals from muscarinic receptors
  • BrdU Labeling index in the gastric mucosa was significantly elevated in H2R–/– mice compared with that in wild-type mice
  • On the other hand, was unable to evoke acid secretion in the mutant mice, suggesting that the mode of action of gastrin for acid secretion depends on H2R-mediated signaling
  • The present study demonstrates the physiological significance of H2 receptor signaling involved in functional regulation of acid secretion as well as gastric architecture, including proliferation and attainment of normal secretory membrane structures of parietal cells

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