Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
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Utilization of Knockout Mice to Examine the Potential Role of Gastric Histamine H2-Receptors in Menetrier's Disease
Toshiki OgawaKazuhiko MaedaShunsuke TonaiTakashi KobayashiTakeshi WatanabeSusumu Okabe
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Volume 91 (2003) Issue 1 Pages 61-70

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Abstract

Menetrier's disease is characterized by giant gastric folds with foveolar hyperplasia and cystic dilatation, hypoproteinemia, and enhanced mucus secretion. The etiology remains unresolved and an effective treatment has yet to be established. Here we show that histamine H2-receptor deficient mice developed gastric pathophysiological changes resembling Menetrier's disease for up to 17 months of observation. Mutant mice were found to have an increased stomach weight, enlarged gastric folds with cystic dilatation, hypergastrinemia, hypoalbuminemia, increased mucus secretion and overexpression of mucosal transforming growth factor (TGF) α. Both a cholecystokinin (CCK)2-receptor antagonist and an epidermal growth factor (EGF)-receptor tyrosine kinase inhibitor significantly reduced the increase in stomach weight. It appears that lack or downregulation of histamine H2-receptors might be involved in the pathogenesis of Menetrier's disease.

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© The Japanese Pharmacological Society 2003
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