Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor–deficient mice

Kobayashi, Takashi; Tonai, Shunsuke; Ishihara, Yasunobu; Koga, Ritsuko; Okabe, Susumu; Watanabe, Takeshi

doi:10.1172/jci9441

Cited by 147 publications

(105 citation statements)

References 34 publications

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“…The functional and morphological changes in the gastric mucosa of such knockout mice has been reported previously (Nagata et al, 1996;Langhans et al, 1997;Friis-Hansen et al, 1998;Kobayashi et al, 2000;Ogawa et al, 2003). A study of gastrin-knockout mice demonstrated that histamine or carbachol administration failed to stimulate acid secretion (Friis-Hansen et al, 1998).…”

Section: Histamine and Gastric Acid Secretion 335mentioning

confidence: 72%

“…Gastric mucosal histamine contents in wild-type and HDC Ϫ/Ϫ mice were measured according to a previously reported method (Kobayashi et al, 2000). In a limited number of mice, mucosal histamine levels were determined 1 h after carbachol or gastrin administration.…”

Section: Animals Male and Female Hdcmentioning

confidence: 99%

“…H 2 -receptor knockout (H 2 R Ϫ/Ϫ ) mice were generated and analyzed in terms of gastric functional and morphological changes (Kobayashi et al, 2000;Ogawa et al, 2003). The basal intragastric pH of H 2 R Ϫ/Ϫ mice was normal (Ͻ3.0).…”

Section: Histamine and Gastric Acid Secretion 335mentioning

confidence: 99%

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

Furutani

Aihara

Nakamura

et al. 2003

J Pharmacol Exp Ther

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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 gastrininduced gastric acid secretion with HDC-knockout (HDC Ϫ/Ϫ ) 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 Ϫ/Ϫ 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 Ϫ/Ϫ 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 Ϫ/Ϫ 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 Ϫ/Ϫ 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.

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Section: Histamine and Gastric Acid Secretion 335mentioning

confidence: 72%

Section: Animals Male and Female Hdcmentioning

confidence: 99%

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

Furutani

Aihara

Nakamura

et al. 2003

J Pharmacol Exp Ther

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“…These mouse genotypes were generated respectively according to the previously described procedures and both WT and KO littermates were identified using PCR [54][55][56].…”

mentioning

confidence: 99%

The brain H3-receptor as a novel therapeutic target for vigilance and sleep–wake disorders

Parmentier

Anaclet

Guhennec³

et al. 2007

Biochemical Pharmacology

155

108

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“…2d). In this scheme, there are various targets of anti-asthma drugs: inhibitions of the "activation" of mast cells [2] and release of chemical mediators [3], receptor # Recent studies using histamine H2 receptor-gene knockout (H2R-KO) mice showed that histamine and ACh are involved in acid secretion and the action of gastrin is mediated through the H2 receptor because gastrin does not cause acid secretion in H2R-KO mice (18). Similar results were obtained in studies using L-histidine decarboxylase (a histamine-forming enzyme) gene-knockout mice (19).…”

Section: Drugs Act In Convergence and Divergencementioning

confidence: 99%

Convergence and Divergence, a Concept for Explaining Drug Actions

Watanabe

Kamisaki

Timmerman³

2004

J Pharmacol Sci

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Abstract. For the teaching and / or learning about drug actions and for the discovery and development of new drugs, it is important to understand how drugs act on living bodies. So far, there has been no clear description on the general principle of drug action in pharmacology textbooks. We propose two principles to depict the action mechanism of drugs. The first is that most, if not all, drugs act on proteins at the molecular level, that is, enzymes, receptors, ion channels, and transporters. The second is that a drug may cause divergent or convergent responses, resulting in changes of a physiological or pathological function of the human body. The concept of divergence and convergence can be used to explain the complex individuality of drug actions.

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Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor–deficient mice

Cited by 147 publications

References 34 publications

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

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

The brain H3-receptor as a novel therapeutic target for vigilance and sleep–wake disorders

Convergence and Divergence, a Concept for Explaining Drug Actions

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