Histamine H3 receptors and the gastric mucosa: a link between protection and epithelial proliferation?

The role of histamine H3 receptors in the control of gastric functions is considered. The selective agonist of histamine H3 receptors, (R)-α-methylhistamine, reduces gastric damage exerted by mechanistically distinct noxious stimuli in the rat. Its effect is reversed by H3-receptor selective antagonists, ciproxifan and clobenpropit, while prevention of damage is similarly achieved with FUB 407, a reference compound for a novel class of histamine H3-receptor agonists structurally not related to histamine. It is concluded that H3 receptors are involved in the maintenance of gastric muscosal integrity. H3 receptors appear to have a minor role in the control of acid secretion, while they effectively enhance synthesis and secretion of mucus as well as increase the number of both surface mucous cells and mucous neck cells. H3 receptors ligands promptly increase the rate of proliferation in the gastric mucosa, their target being stem cells located in the isthmal region. They also influence the process of differentiation, by promoting the expansion of the lineage of surface mucous cells. Prevention of acute damage and regulation of cell cycle of gastric epithelial cells can be viewed as functionally linked effects, influenced by histamine H3 receptors.