Gastrin interferes with the differentiation of gastric pit cells and parietal cells.

Abstract

Gastrin is known to have stimulatory effects on gastric mucosa; however, long-term effect of gastrin stimulation is not well known. 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. 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. 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.