title: Histamine 3 receptor activation mediates inhibition of acid secretion during Helicobacter-induced gastritis.
abstract: OBJECTIVE
  To test the hypothesis that histamine 3 receptor (H3R) activation during Helicobacter infection inhibits gastric acid secretion in vivo and in vitro.
  
  
  METHODS
  Helicobacter felis (H. felis) infected and uninfected C57Bl/6 mice were infused with either PBS or the H3 receptor antagonist thioperamide (THIO) for 12 wk. After treatment, mice were analyzed for morphological changes and gastric acid content. Total RNA was prepared from the stomachs of each group and analyzed for changes in somatostatin and gastrin mRNA abundance by real time-polymerase chain reaction (RT-PCR). Location of H3 receptors in the stomach was analyzed by co-localization using antibodies specific for the H3 receptor and parietal cell marker H(+), K(+)-ATPase β subunit.
  
  
  RESULTS
  Inflammation and parietal cell atrophy was observed after 12 wk of H. felis infection. Interestingly, treatment with the H3R antagonist thioperamide (THIO) prior to and during infection prevented H. felis-induced inflammation and atrophy. Compared to the uninfected controls, infected mice also had significantly decreased gastric acid. After eradication of H. felis with THIO treatment, gastric acidity was restored. Compared to the control mice, somatostatin mRNA abundance was decreased while gastrin gene expression was elevated during infection. Despite elevated gastric acid levels, after eradication of H. felis with THIO, somatostatin mRNA was elevated whereas gastrin mRNA was suppressed. Immunofluorescence revealed the presence of H3 receptors on the parietal cells, somatostatin-secreting D-cells as well as the inflammatory cells.
  
  
  CONCLUSIONS
  This study shows that during H. felis infection, gastric acidity is suppressed as a consequence of an inhibitory effect on the parietal cell by H3R activation. The stimulation of gastric mucosal H3Rs increases gastrin expression and release by inhibiting release of somatostatin.
authors: Yana Zavros, Nisreen Mesiwala, Meghna Waghray, Andrea Todisco, Juanita L Merchant, Departments of Internal Medicine-Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109-2200, United States.
authors: Yana
authors: Y
authors: Zavros
authors: Nisreen
authors: N
authors: Mesiwala
authors: Meghna
authors: M
authors: Waghray
authors: Andrea
authors: A
authors: Todisco
authors: Arthur
authors: A
authors: Shulkes
authors: Juanita L
authors: JL
authors: Merchant
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