Expanded parietal cell pool in transgenic mice unable to synthesize histamine

B. Hunyady, A. Zólyomi, J. Czimmer, G. Mózsik, T. Kozicz, E. Buzás, S. Tanaka, A. Ichikawa, A. Nagy, M. Palkovits, A. Falus

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10 Citations (Scopus)

Abstract

Background: The histidine decarboxylase enzyme (HDC) is responsible for the synthesis of histamine in mammals. Histidine decarboxylase-deficient (HDC-/-) mice have recently been developed by targeted mutation of the HDC gene. Methods: The impact of prolonged histamine deficiency was studied on gastric morphology (by immunohistochemistry and morphometry), gastric acid secretion (by a washthrough method for basal gastric acid secretion and by pylorus ligation for stimulated gastric acid secretion) and gastrin levels (by radioimmunoassay) in homozygous HDC-/- mice kept on a low-histamine diet. Results: A double maximal gastric acid secretory response was found in knockouts after exogenous histamine administration. In contrast, the gastric acid secretion was significantly reduced after gastrinergic and cholinergic stimulation in the absence of histamine. The oxynthic gland area of HDC-/- mice was thickened with an increased parietal cell count compared to wild types. Substantially elevated serum and antral tissue gastrin levels of HDC-/- mice could be possible indications of both an expanded parietal cell mass and/or an increased histamine-induced maximal gastric acid secretory capacity of this genotype. Conclusions: These data suggest that not enough compensatory mechanisms develop in HDC-/- mice during a prolonged low-histamine diet to maintain/restore normal gastric acid secretion. An expanded parietal cell pool was also demonstrated in HDC-/- mice kept on a low-histamine diet, probably caused by atrophic effect of sustained hypergastrinaemia. The HDC-/- strain is a suitable model for studying the effects of achlorhydria and consequent hypergastrinaemia as an approach to human conditions such as atrophic gastritis or long-term antisecretory therapies.

Original languageEnglish
Pages (from-to)133-140
Number of pages8
JournalScandinavian Journal of Gastroenterology
Volume38
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

Keywords

  • Gastric acid secretion
  • Gastrin
  • Histamine
  • Histidine decarboxylase enzyme
  • Immunohistochemistry
  • Transgenic mice

ASJC Scopus subject areas

  • Gastroenterology

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    Hunyady, B., Zólyomi, A., Czimmer, J., Mózsik, G., Kozicz, T., Buzás, E., Tanaka, S., Ichikawa, A., Nagy, A., Palkovits, M., & Falus, A. (2003). Expanded parietal cell pool in transgenic mice unable to synthesize histamine. Scandinavian Journal of Gastroenterology, 38(2), 133-140. https://doi.org/10.1080/gas.38.2.133