Abstract
Spasmolytic polypeptide (SP/TFF2)-expressing metaplasia (SPEM) is induced by oxyntic atrophy and is known as a precancerous or paracancerous lesion. We seek to determine whether the gastrin receptor or H(2) histamine receptor influence the development of SPEM. DMP-777 was administered to gastrin receptor and/or H(2) receptor-deficient mice and wild-type mice. Gastric mucosal lineage changes were analyzed. The mucosa from double knockout mice and H(2) receptor knockout mice contained elevated numbers of dual TFF2 and intrinsic factor immunoreactive cells even before DMP-777 treatment. All genotypes of mice showed SPEM after 7-day treatment. In all types of knockout mice, the number of TFF2 immunoreactive cells remained elevated after cessation of treatment. The H(2) receptor and gastrin receptor do not affect emergence of SPEM. However, it is suggested that the absence of H(2) receptor signaling causes a delay in the maturation of chief cells from mucous neck cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Atrophy / chemically induced
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Atrophy / pathology
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Azetidines / adverse effects
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Azetidines / pharmacology
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Cell Differentiation / drug effects
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Cell Lineage* / drug effects
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Cell Proliferation / drug effects
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Gastric Mucosa / cytology*
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Gastric Mucosa / metabolism
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Gastrins / blood
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Intrinsic Factor / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mucins / metabolism
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Muscle Proteins / metabolism
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Parietal Cells, Gastric / metabolism
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Parietal Cells, Gastric / pathology*
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Peptides / metabolism
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Piperazines / adverse effects
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Piperazines / pharmacology
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Receptor, Cholecystokinin B / genetics
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Receptor, Cholecystokinin B / metabolism*
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Receptors, Histamine H2 / genetics
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Receptors, Histamine H2 / metabolism*
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Trefoil Factor-2
Substances
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Azetidines
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Gastrins
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Mucins
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Muscle Proteins
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Peptides
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Piperazines
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Receptor, Cholecystokinin B
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Receptors, Histamine H2
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TFF2 protein, mouse
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Trefoil Factor-2
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DMP 777
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Intrinsic Factor