QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.052019v1 307/1/331    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Furutani, K. Articles by Okabe, S. Search for Related Content PubMed PubMed Citation Articles by Furutani, K. Articles by Okabe, S.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Crucial Role of Histamine for Regulation of Gastric Acid Secretion Ascertained by Histidine Decarboxylase-Knockout Mice

Department of Applied Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan (K.F., T.A., E.N., S.O.); Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan (S.T., A.I.); and Department of Cellular Pharmacology, Tohoku University School of Medicine, Sendai, Japan (H.O.)

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.

Address correspondence to: Dr. Susumu Okabe, Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan. E-mail: okabe{at}mb.kyoto-phu.ac.jp

This article has been cited by other articles:

				K.-i. Tanaka, S. Tsutsumi, Y. Arai, T. Hoshino, K. Suzuki, E. Takaki, T. Ito, K. Takeuchi, A. Nakai, and T. Mizushima Genetic Evidence for a Protective Role of Heat Shock Factor 1 against Irritant-Induced Gastric Lesions Mol. Pharmacol., April 1, 2007; 71(4): 985 - 993. [Abstract] [Full Text] [PDF]

				D. Chen, T. Aihara, C.-M. Zhao, R. Hakanson, and S. Okabe Differentiation of the Gastric Mucosa I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes. Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G539 - G544. [Abstract] [Full Text] [PDF]

				T. Aihara, Y. Nakamura, M. M. Taketo, M. Matsui, and S. Okabe Cholinergically stimulated gastric acid secretion is mediated by M3 and M5 but not M1 muscarinic acetylcholine receptors in mice Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1199 - G1207. [Abstract] [Full Text] [PDF]

				E. Nakamura, T. Kataoka, K. Furutani, K. Jimbo, T. Aihara, S. Tanaka, A. Ichikawa, H. Ohtsu, and S. Okabe Lack of histamine alters gastric mucosal morphology: comparison of histidine decarboxylase-deficient and mast cell-deficient mice Am J Physiol Gastrointest Liver Physiol, November 1, 2004; 287(5): G1053 - G1061. [Abstract] [Full Text] [PDF]