Histamine, acting via H3 receptors, inhibits somatostatin and stimulates acid secretion in isolated mouse stomach

Gastroenterology. 1997 Nov;113(5):1545-52. doi: 10.1053/gast.1997.v113.pm9352856.


Background & aims: The role of histamine H3 receptors in the regulation of gastric acid secretion is unclear. The present study was designed to characterize the location of H3 receptors in the fundus of the stomach and the mechanism by which these receptors regulate acid secretion.

Methods: Acid, somatostatin, and histamine secretions were measured in the isolated mouse stomach.

Results: Thioperamide (H3 antagonist) increased somatostatin and decreased histamine and acid secretion in a concentration-dependent manner. (r)-alpha-Methylhistamine (H3 agonist) had the opposite effect, decreasing somatostatin and increasing histamine and acid secretion. The pattern implies that endogenous histamine, acting via H3 receptors, exerts an inhibitory paracrine influence on somatostatin secretion. Somatostatin antibody increased basal histamine secretion and abolished the decrease in histamine and acid secretion induced by thioperamide, confirming that changes in histamine and acid secretion induced by the activation of H3 receptors reflected changes in somatostatin secretion. Similar effects were obtained when acid secretion was stimulated by histamine: thioperamide augmented somatostatin and thus inhibited acid secretion, and (r)-alpha-methylhistamine attenuated somatostatin and increased acid secretion.

Conclusions: Reciprocal inhibitory paracrine pathways link histamine and somatostatin cells in the gastric fundus. Histamine, acting via H3 receptors, augments acid secretion by eliminating the inhibitory influence of somatostatin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Gastric Acid / metabolism*
  • Gastric Mucosa / drug effects
  • Histamine / pharmacology*
  • Histamine Release / drug effects
  • In Vitro Techniques
  • Male
  • Mice
  • Perfusion
  • Receptors, Histamine H3 / physiology*
  • Somatostatin / metabolism*
  • Somatostatin / pharmacology


  • Receptors, Histamine H3
  • Somatostatin
  • Histamine