Premium
Gastrin interferes with the differentiation of gastric pit cells and parietal cells
Author(s) -
Nakajima T.,
Konda Y.,
Izumi Y.,
Kanai M.,
Takeuchi T.,
Chiba T.
Publication year - 2002
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.16.s2.25.x
Subject(s) - gastrin , medicine , endocrinology , g cell , transgene , gastric mucosa , parietal cell , genetically modified mouse , enterochromaffin like cell , stimulation , biology , receptor , gastric chief cell , in situ hybridization , stomach , messenger rna , secretion , gene , biochemistry
Background: Gastrin is known to have stimulatory effects on gastric mucosa; however, long‐term effect of gastrin stimulation is not well known. Aim and methods: To investigate the long‐term effect of hypergastrinaemia, we established hypergastrinaemic transgenic mice by introducing a mutated human gastrin gene. Homozygously transgene‐expressing mice showed serum gastrin levels of more than 600 pg/mL. Results: Neither progastrin nor glycine‐extended gastrin titre elevation were observed in hypergastrinaemic transgenic mice. Stomachs from the 30–35‐week‐old transgenic mice were 30–50% heavier and their mucosa were markedly thicker than those of the controls. The hypertrophic gastric mucosa of hypergastrinaemic transgenic mice consisted of elongated pits with widespread proliferative zones, and comprised depleted glandular regions. In situ hybridization study indicated that expression of H, K‐ATPase mRNA in parietal cells of hypergastrinaemic transgenic mice was markedly decreased. By gastrin binding assay in vivo , specific gastrin binding sites were observed in the mid‐glandular region of hypergastrinaemic transgenic mice that consisted mainly of prepit cells. Conclusions: These results suggest that long‐term stimulation of gastrin increases the expression of CCK‐B/gastrin receptors in the less‐differentiated pit cells that are the main component of elongated gastric units, and lessens the well‐differentiated characteristics of parietal cells.