| First Author | Furutani K | Year | 2003 |
| Journal | J Pharmacol Exp Ther | Volume | 307 |
| Issue | 1 | Pages | 331-8 |
| PubMed ID | 12893847 | Mgi Jnum | J:123457 |
| Mgi Id | MGI:3718332 | Doi | 10.1124/jpet.103.052019 |
| Citation | Furutani K, et al. (2003) Crucial role of histamine for regulation of gastric acid secretion ascertained by histidine decarboxylase-knockout mice. J Pharmacol Exp Ther 307(1):331-8 |
| abstractText | 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 H2-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. |
