Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor-deficient mice.
J Clin Invest
; 105(12): 1741-9, 2000 Jun.
Article
em En
| MEDLINE
| ID: mdl-10862789
ABSTRACT
To clarify the physiological roles of histamine H2 receptor (H2R), we have generated histamine H2R-deficient mice by gene targeting. Homozygous mutant mice were viable and fertile without apparent abnormalities and, unexpectedly, showed normal basal gastric pH. However, the H2R-deficient mice exhibited a marked hypertrophy with enlarged folds in gastric mucosa and an elevated serum gastrin level. Immunohistochemical analysis revealed increased numbers of parietal and enterochromaffin-like (ECL) cells. Despite this hypertrophy, parietal cells in mutant mice were significantly smaller than in wild-type mice and contained enlarged secretory canaliculi with a lower density of microvilli and few typical tubulovesicles in the narrow cytoplasm. Induction of gastric acid secretion by histamine or gastrin was completely abolished in the mutant mice, but carbachol still induced acid secretion. The present study clearly demonstrates that H2R-mediated signal(s) are required for cellular homeostasis of the gastric mucosa and normally formed secretory membranes in parietal cells. Moreover, impaired acid secretion due to the absence of H2R could be overcome by the signals from cholinergic receptors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Histamínicos H2
/
Mucosa Gástrica
Limite:
Animals
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Japão