Crucial role of histamine for regulation of gastric acid secretion ascertained by histidine decarboxylase-knockout mice

Kazuharu Furutani, Takeshi Aihara, Eiji Nakamura, Satoshi Tanaka, Atsushi Ichikawa, Hiroshi Ohtsu, Susumu Okabe

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Histidine decarboxylase (HDC) represents the sole enzyme that produces histamine in the body. The present work investigated the role of endogenous histamine in carbachol- and gastrin-induced gastric acid secretion with HDC-knockout (HDC-/-) mice. Acid secretion was measured in either mice subjected to acute fistula production under urethane anesthesia or conscious mice that had previously undergone pylorus ligation. In wild-type mice, carbachol and gastrin significantly stimulated acid secretion, increasing gastric mucosal histamine. In contrast, in HDC-/- mice, carbachol and gastrin had little impact when either delivered alone or together. Nonetheless, the two agents achieved a synergistic effect when delivered together with exogenous histamine, stimulating acid secretion in HDC -/- mice. Such synergism was abolished by the histamine H 2-receptor antagonist famotidine. cAMP involvement in acid secretion was also examined with theophylline, a phosphodiesterase inhibitor, and forskolin, an adenylate cyclase activator. In wild-type mice, theophylline significantly increased acid secretion, enhancing carbachol- and gastrin-stimulated acid secretion. In contrast, in HDC-/- mice, theophylline failed to exert an effect on basal acid secretion, as well as carbachol- and gastrin-stimulated acid secretion. Although forskolin interacted with carbachol, allowing acid secretion in HDC-/- mice, similar results were not achieved with gastrin. Such results suggest that 1) histamine is essential for carbachol- and gastrin-stimulated gastric acid secretion in mice; and 2) histamine-induced cAMP production contributes to the in vivo response to carbachol or gastrin.

Original languageEnglish (US)
Pages (from-to)331-338
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume307
Issue number1
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this