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PMID:15476751

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Citation

Fukushima, Y, Matsui, T, Saitoh, T, Ichinose, M, Tateishi, K, Shindo, T, Fujishiro, M, Sakoda, H, Shojima, N, Kushiyama, A, Fukuda, S, Anai, M, Ono, H, Oka, M, Shimizu, Y, Kurihara, H, Nagai, R, Ishikawa, T, Asano, T and Omata, M (2004) Unique roles of G protein-coupled histamine H2 and gastrin receptors in growth and differentiation of gastric mucosa. Eur. J. Pharmacol. 502:243-52

Abstract

Disruption of histamine H2 receptor and gastrin receptor had different effects growth of gastric mucosa: hypertrophy and atrophy, respectively. To clarify the roles of gastrin and histamine H2 receptors in gastric mucosa, mice deficient in both (double-null mice) were generated and analyzed. Double-null mice exhibited atrophy of gastric mucosae, marked hypergastrinemia and higher gastric pH than gastrin receptor-null mice, which were unresponsive even to carbachol. Comparison of gastric mucosae from 10-week-old wild-type, histamine H2 receptor-null, gastrin receptor-null and double-null mice revealed unique roles of these receptors in gastric mucosal homeostasis. While small parietal cells and increases in the number and mucin contents of mucous neck cells were secondary to impaired acid production, the histamine H2 receptor was responsible for chief cell maturation in terms of pepsinogen expression and type III mucin. In double-null and gastrin receptor-null mice, despite gastric mucosal atrophy, surface mucous cells were significantly increased, in contrast to gastrin-null mice. Thus, it is conceivable that gastrin-gene product(s) other than gastrin-17, in the stimulated state, may exert proliferative actions on surface mucous cells independently of the histamine H2 receptor. These findings provide evidence that different G-protein coupled-receptors affect differentiation into different cell lineages derived from common stem cells in gastric mucosa.

Links

PubMed Online version:10.1016/j.ejphar.2004.09.013

Keywords

Animals; Atrophy; Carbachol/administration & dosage; Cell Differentiation/drug effects; Cell Differentiation/physiology; Cell Lineage/drug effects; Cell Lineage/physiology; Cell Proliferation/drug effects; Female; Gastric Acidity Determination; Gastric Mucosa/cytology; Gastric Mucosa/drug effects; Gastric Mucosa/growth & development; Gastric Mucosa/pathology; Gastrins/administration & dosage; Histamine/administration & dosage; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptor, Cholecystokinin B/deficiency; Receptor, Cholecystokinin B/genetics; Receptor, Cholecystokinin B/physiology; Receptors, Histamine H2/deficiency; Receptors, Histamine H2/genetics; Receptors, Histamine H2/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GASR

involved_in

GO:0001696: gastric acid secretion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:108482

P

Seeded From UniProt

complete

MOUSE:GASR

involved_in

GO:0048565: digestive tract development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2384535

P

Seeded From UniProt

complete

MOUSE:GASR

involved_in

GO:0048732: gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2384535

P

Seeded From UniProt

complete

MOUSE:GASR

involved_in

GO:0001696: gastric acid secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2384535

P

Seeded From UniProt

complete

MOUSE:HRH2

involved_in

GO:0001696: gastric acid secretion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:99479

P

Seeded From UniProt

complete

MOUSE:HRH2

involved_in

GO:0048565: digestive tract development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3607154

P

Seeded From UniProt

complete

MOUSE:HRH2

involved_in

GO:0048732: gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3607154

P

Seeded From UniProt

complete

MOUSE:HRH2

involved_in

GO:0001697: histamine-induced gastric acid secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3607154

P

Seeded From UniProt

complete

MOUSE:HRH2

involved_in

GO:0001698: gastrin-induced gastric acid secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3607154

P

Seeded From UniProt

complete

MOUSE:GASR

acts_upstream_of_or_within

GO:0048565: digestive tract development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2384535

P

Seeded From UniProt

complete

MOUSE:GASR

acts_upstream_of_or_within

GO:0048732: gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2384535

P

Seeded From UniProt

complete

MOUSE:GASR

acts_upstream_of_or_within

GO:0001696: gastric acid secretion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:108482

P

Seeded From UniProt

complete

MOUSE:GASR

acts_upstream_of_or_within

GO:0001696: gastric acid secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2384535

P

Seeded From UniProt

complete


See also

References

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