Histamine H_3 receptors and the gastric mucosa: A link between protection and epithelial proliferation?

摘要

The role of histamine H_3 receptors in the control of gastric functions is considered. The selective agonist of histamine H_3 receptors, (R)-oc-methylhistamine, reduces gastric damage exerted by mechanistically distinct noxious stimuli in the rat. Its effect is reversed by H_3-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 H_3-receptor agonists structurally not related to histamine. It is concluded that H_3 receptors are involved in the maintenance of gastric muscosal integrity. H_3 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. H_3 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 processof 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 H_3 receptors.