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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.

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Related in: MedlinePlus

Regulation of PGE receptor gene expressions. A. Constitutive expression of PGE receptor genes in different cell types of kidney. Schematic representation of the distribution of PGE receptors in the nephron (center panel). EP1 is expressed in the collecting duct (blue), EP3 is expressed in thick ascending limb (yellow), and EP4 is expressed in the glomerulus (red). EP1 and EP3 are involved in inhibition of water and ion transport, respectively. EP4 is involved in regulation of glomerular filtration rate. B. Inducible gene expression of COX-2 and the EP2 receptor in cumulus cells (hormonal stimuli) or macrophage (proinflammatory stimuli). In these cells, gene expression of COX-2 and EP2 is induced in a similar manner. As a result, COX-2-derived PGE2 acts on the EP2 receptor, and elicits functional changes via the Gs/cAMP/PKA pathway in an autocrine fashion.
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fig06: Regulation of PGE receptor gene expressions. A. Constitutive expression of PGE receptor genes in different cell types of kidney. Schematic representation of the distribution of PGE receptors in the nephron (center panel). EP1 is expressed in the collecting duct (blue), EP3 is expressed in thick ascending limb (yellow), and EP4 is expressed in the glomerulus (red). EP1 and EP3 are involved in inhibition of water and ion transport, respectively. EP4 is involved in regulation of glomerular filtration rate. B. Inducible gene expression of COX-2 and the EP2 receptor in cumulus cells (hormonal stimuli) or macrophage (proinflammatory stimuli). In these cells, gene expression of COX-2 and EP2 is induced in a similar manner. As a result, COX-2-derived PGE2 acts on the EP2 receptor, and elicits functional changes via the Gs/cAMP/PKA pathway in an autocrine fashion.

Mentions: Among the four PGE receptors, EP3 and EP4 receptors are widely distributed throughout the body, with their mRNAs being expressed in almost all mouse tissues examined. In contrast, the distribution of EP1 mRNA is restricted to several organs such as the kidney, lung and stomach, and EP2 is the least abundant among the EP receptors. In general, the PGE receptor subtypes show ‘distinct’ cellular localizations. For example, in the kidney, we found that EP3 receptor is expressed in the tubular epithelium of the outer medulla, especially in the thick ascending limb and cortical collecting ducts, EP1 receptor in the papillary collecting ducts and EP4 receptor in the glomerulus (Fig. 6A).75) The distribution pattern appears to correspond with the PGE2-mediated regulation of ion transport, water reabsorption and glomerular filtration, respectively. However, there was no expression of EP2 mRNA.


Molecular biology of histidine decarboxylase and prostaglandin receptors.

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

Regulation of PGE receptor gene expressions. A. Constitutive expression of PGE receptor genes in different cell types of kidney. Schematic representation of the distribution of PGE receptors in the nephron (center panel). EP1 is expressed in the collecting duct (blue), EP3 is expressed in thick ascending limb (yellow), and EP4 is expressed in the glomerulus (red). EP1 and EP3 are involved in inhibition of water and ion transport, respectively. EP4 is involved in regulation of glomerular filtration rate. B. Inducible gene expression of COX-2 and the EP2 receptor in cumulus cells (hormonal stimuli) or macrophage (proinflammatory stimuli). In these cells, gene expression of COX-2 and EP2 is induced in a similar manner. As a result, COX-2-derived PGE2 acts on the EP2 receptor, and elicits functional changes via the Gs/cAMP/PKA pathway in an autocrine fashion.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig06: Regulation of PGE receptor gene expressions. A. Constitutive expression of PGE receptor genes in different cell types of kidney. Schematic representation of the distribution of PGE receptors in the nephron (center panel). EP1 is expressed in the collecting duct (blue), EP3 is expressed in thick ascending limb (yellow), and EP4 is expressed in the glomerulus (red). EP1 and EP3 are involved in inhibition of water and ion transport, respectively. EP4 is involved in regulation of glomerular filtration rate. B. Inducible gene expression of COX-2 and the EP2 receptor in cumulus cells (hormonal stimuli) or macrophage (proinflammatory stimuli). In these cells, gene expression of COX-2 and EP2 is induced in a similar manner. As a result, COX-2-derived PGE2 acts on the EP2 receptor, and elicits functional changes via the Gs/cAMP/PKA pathway in an autocrine fashion.
Mentions: Among the four PGE receptors, EP3 and EP4 receptors are widely distributed throughout the body, with their mRNAs being expressed in almost all mouse tissues examined. In contrast, the distribution of EP1 mRNA is restricted to several organs such as the kidney, lung and stomach, and EP2 is the least abundant among the EP receptors. In general, the PGE receptor subtypes show ‘distinct’ cellular localizations. For example, in the kidney, we found that EP3 receptor is expressed in the tubular epithelium of the outer medulla, especially in the thick ascending limb and cortical collecting ducts, EP1 receptor in the papillary collecting ducts and EP4 receptor in the glomerulus (Fig. 6A).75) The distribution pattern appears to correspond with the PGE2-mediated regulation of ion transport, water reabsorption and glomerular filtration, respectively. However, there was no expression of EP2 mRNA.

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
Related in: MedlinePlus