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Molecular biology of histidine decarboxylase and prostaglandin receptors.

Ichikawa A, Sugimoto Y, Tanaka S - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses.We then characterized the expression patterns and functions of these genes.We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. aichikaw@mukogawa-u.ac.jp

ABSTRACT
Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in the body. They stimulate target cells by acting on their specific receptors, which are coupled to trimeric G proteins. For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses. We cloned the cDNAs for mouse L-histidine decarboxylase (HDC) and 6 mouse prostanoid receptors (4 PGE(2) receptors, PGF receptor, and PGI receptor). We then characterized the expression patterns and functions of these genes. Furthermore, we established gene-targeted mouse strains for HDC and PG receptors to explore the novel pathophysiological roles of histamine and PGs. We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.

Show MeSH
Roles of histamine in gastric acid secretion. Histamine, acetylcholine (muscarinic), and gastrin are major secretagogues in gastric acid secretion. Accumulating evidence suggests that acetylcholine and gastrin stimulate histamine release from ECL cells, which synergistically enhance the acid secretion through direct stimulation of parietal cells by these secretagogues. Massive and prolonged acid secretion by gastrin was found to require transcriptional activation of the HDC gene. Investigation using the HDC−/− mice revealed that histamine plays a critical role in gastrin-mediated acid secretion but not in muscarinic acid secretion.
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fig03: Roles of histamine in gastric acid secretion. Histamine, acetylcholine (muscarinic), and gastrin are major secretagogues in gastric acid secretion. Accumulating evidence suggests that acetylcholine and gastrin stimulate histamine release from ECL cells, which synergistically enhance the acid secretion through direct stimulation of parietal cells by these secretagogues. Massive and prolonged acid secretion by gastrin was found to require transcriptional activation of the HDC gene. Investigation using the HDC−/− mice revealed that histamine plays a critical role in gastrin-mediated acid secretion but not in muscarinic acid secretion.

Mentions: Histamine is one of the critical acid secretagogues in the stomach. We then investigated gastric acid secretion in HDC−/− mice.44) HDC−/− mice were found to be sensitive to exogenous histamine but were resistant to gastrin, which induces gastric acid secretion. Our study revealed the roles of histamine in gastric acid secretion induced by muscarinic stimulation and gastrin (Fig. 3). HDC−/− mice exhibited similar features to mice continuously treated with H2R antagonists, such as hypergastrinemia and acid hypersecretion in response to histamine. Although H2R−/− mice shared many features with HDC−/− mice, such as hypergastrinemia, a marked hypertrophy with enlarged folds of the gastric mucosa was observed only in the H2R−/− mice.45) These results suggested that histamine is involved in the maintenance of gastric mucosal cellular composition.


Molecular biology of histidine decarboxylase and prostaglandin receptors.

Ichikawa A, Sugimoto Y, Tanaka S - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Roles of histamine in gastric acid secretion. Histamine, acetylcholine (muscarinic), and gastrin are major secretagogues in gastric acid secretion. Accumulating evidence suggests that acetylcholine and gastrin stimulate histamine release from ECL cells, which synergistically enhance the acid secretion through direct stimulation of parietal cells by these secretagogues. Massive and prolonged acid secretion by gastrin was found to require transcriptional activation of the HDC gene. Investigation using the HDC−/− mice revealed that histamine plays a critical role in gastrin-mediated acid secretion but not in muscarinic acid secretion.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037517&req=5

fig03: Roles of histamine in gastric acid secretion. Histamine, acetylcholine (muscarinic), and gastrin are major secretagogues in gastric acid secretion. Accumulating evidence suggests that acetylcholine and gastrin stimulate histamine release from ECL cells, which synergistically enhance the acid secretion through direct stimulation of parietal cells by these secretagogues. Massive and prolonged acid secretion by gastrin was found to require transcriptional activation of the HDC gene. Investigation using the HDC−/− mice revealed that histamine plays a critical role in gastrin-mediated acid secretion but not in muscarinic acid secretion.
Mentions: Histamine is one of the critical acid secretagogues in the stomach. We then investigated gastric acid secretion in HDC−/− mice.44) HDC−/− mice were found to be sensitive to exogenous histamine but were resistant to gastrin, which induces gastric acid secretion. Our study revealed the roles of histamine in gastric acid secretion induced by muscarinic stimulation and gastrin (Fig. 3). HDC−/− mice exhibited similar features to mice continuously treated with H2R antagonists, such as hypergastrinemia and acid hypersecretion in response to histamine. Although H2R−/− mice shared many features with HDC−/− mice, such as hypergastrinemia, a marked hypertrophy with enlarged folds of the gastric mucosa was observed only in the H2R−/− mice.45) These results suggested that histamine is involved in the maintenance of gastric mucosal cellular composition.

Bottom Line: For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses.We then characterized the expression patterns and functions of these genes.We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. aichikaw@mukogawa-u.ac.jp

ABSTRACT
Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in the body. They stimulate target cells by acting on their specific receptors, which are coupled to trimeric G proteins. For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses. We cloned the cDNAs for mouse L-histidine decarboxylase (HDC) and 6 mouse prostanoid receptors (4 PGE(2) receptors, PGF receptor, and PGI receptor). We then characterized the expression patterns and functions of these genes. Furthermore, we established gene-targeted mouse strains for HDC and PG receptors to explore the novel pathophysiological roles of histamine and PGs. We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.

Show MeSH