PMID:15476751

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
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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

References

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