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Structural and functional characterization of gastric mucosa and central nervous system in histamine H2 receptor-null mice.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2003 May 02; Vol. 468 (1), pp. 47-58. - Publication Year :
- 2003
-
Abstract
- To examine the physiological role of the histamine H(2) receptor, histamine H(2) receptor-null mice were generated by homologous recombination. Histamine H(2) receptor-null mice, which developed normally and were fertile and healthy into adulthood, exhibited markedly enlarged stomachs and marked hypergastrinemia. The former was due to hyperplasia of gastric gland cells (small-sized parietal cells, enterochromaffin-like cells and mucous neck cells which were rich in mucin), but not of gastric surface mucous cells, which were not increased in number as compared with those in wild-type mice despite the marked hypergastrinemia. Basal gastric pH was slightly but significantly higher in histamine H(2) receptor-null mice. Although carbachol but not gastrin induced in vivo gastric acid production in histamine H(2) receptor-null mice, gastric pH was elevated by both muscarinic M(3) and gastrin antagonists. Thus, both gastrin and muscarinic receptors appear to be directly involved in maintaining gastric pH in histamine H(2) receptor-null mice. Interestingly, gastric glands from wild-type mice treated with an extremely high dose of subcutaneous lansoprazole (10 mg/kg body weight) for 3 months were very similar to those from histamine H(2) receptor-null mice. Except for hyperplasia of gastric surface mucous cells, the findings for gastric glands from lansoprazole-treated wild-type mice were almost identical to those from gastric glands from histamine H(2) receptor-null mice. Therefore, it is possible that the abnormal gastric glands in histamine H(2) receptor-null mice are secondary to the severe impairment of gastric acid production, induced by the histamine H(2) receptor disruption causing marked hypergastrinemia. Analyses of the central nervous system (CNS) of histamine H(2) receptor-null mice revealed these mice to be different from wild-type mice in terms of spontaneous locomotor activity and higher thresholds for electrically induced convulsions. Taken together, these results suggest that (1) gastrin receptors are functional in parietal cells in histamine H(2) receptor-null mice, (2) abnormal gastric glands in histamine H(2) receptor-null mice may be secondary to severe impairment of gastric acid production and secretion and (3) histamine H(2) receptors are functional in the central nervous system.
- Subjects :
- 2-Pyridinylmethylsulfinylbenzimidazoles
Animals
Blotting, Northern
Electroshock
Gastric Acid metabolism
Gastric Mucosa cytology
Gastric Mucosa metabolism
Gastrins blood
Gene Targeting
Hydrogen-Ion Concentration
Hyperplasia
Immunohistochemistry
Lansoprazole
Mice
Omeprazole analogs & derivatives
Omeprazole pharmacology
Pain Threshold
Proton Pump Inhibitors
Receptors, Histamine H2 deficiency
Receptors, Histamine H2 genetics
Seizures chemically induced
Gastric Mucosa pathology
Receptors, Histamine H2 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 468
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 12729842
- Full Text :
- https://doi.org/10.1016/s0014-2999(03)01668-6