Molecular Cloning and Expression of a Rat Prostaglandin E2 Receptor of the EP2 Subtype

Nemoto, Koji; Pilbeam, Carol C.; Bilak, Stephan R.; Raisz, Lawrence G.

doi:10.1016/s0090-6980(97)00145-7

Cited by 70 publications

(44 citation statements)

References 16 publications

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“…There are pharmacologically four kinds of receptor subtypes of PGE2, namely EP1 to EP4, and that cDNA is cloned for each receptor subtype (19,20). All the receptor subtypes were demonstrated to be expressed in the kidney (21,22). Expression of EP 2-and EP4-receptor mRNA in mouse glomeruli was demonstrated by RT-PCR assay.…”

Section: Discussionmentioning

confidence: 92%

Involvement of Prostaglandin E2 in Clearance of Aggregated Protein via Protein Kinase A in Glomeruli

Nagamatsu

Nagao

Koseki

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-Recently we immunohistochemically demonstrated that prostaglandin E2 (PGE2) promoted the clearance of aggregated bovine serum albumin (a-BSA) deposited in glomeruli. Herein, we investigated the role of PGE2 and its signal transduction in the disposal of macromolecules in glomeruli. EP2 and EP4 receptor mRNA was detected in glomeruli by RT-PCR analysis. A-BSA was injected twice into mice. Glomeruli were then isolated and incubated. A-BSA gradually disappeared from isolated glomeruli. PGE 2 increased the intracellular cyclic AMP and decreased a-BSA level in glomeruli. Additionally, 8-bromocyclic AMP evoked a loss of a-BSA in isolated glomeruli. The effect of 8-bromo-cyclic AMP on the clearance of a-BSA was abolished by KT 5720 in glomeruli. PGE2 and 8-bromo-cyclic AMP also prompted disposal of a-BSA in cultured mesangial cells. These findings indicate that PGE2 positively regulates the removal of macromolecules via cyclic AMP and protein kinase A in glomeruli, and they provide insight into how to prevent the development of glomerulonephritis and glomerulosclerosis.

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Section: Discussionmentioning

confidence: 92%

Involvement of Prostaglandin E2 in Clearance of Aggregated Protein via Protein Kinase A in Glomeruli

Nagamatsu

Nagao

Koseki

et al. 2001

Japanese Journal of Pharmacology

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“…It has been demonstrated in experimental models of nephritis that the production of prostaglandin E 2 increases in nephritic glomeruli and excretion of prostaglandin E 2 into urine also increases (2 -4). Pharmacologically, there are four kinds of prostaglandin E 2 -receptor subtypes, namely, EP 1 , EP 2 , EP 3 , and EP 4 ; and the expression of mRNA of all four receptor subtypes has been demonstrated in the kidney (5,6). We have previously demonstrated the expression of mRNA of EP 2 and EP 4 in the glomeruli by reverse transcription polymerase chain reaction (RT-PCR) analysis (7).…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Prostaglandin EP4-Receptor Agonist on Anti-glomerular Basement Membrane Antibody-Associated Nephritis

et al. 2006

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Abstract. Prostaglandin E 2 -receptor subtypes, EP 1 , EP 2 , EP 3 , and EP 4 , are present in the kidney. The aim of this study was to elucidate the anti-nephritic effect of an EP 4 -receptor agonist on an experimental nephritic model. Mice were injected i.v. with anti-glomerulus antiserum to induce nephritis. Nephritic glomeruli generated more prostaglandin E 2 (2.6 and 0.7 ng) and less cyclic AMP than normal glomeruli (11 and 26 pmol). The production of cyclic AMP in nephritic glomeruli increased 67% in response to AE1-329, an EP 4 agonist, at 10 −5 M. Nephritic glomeruli expressed a lesser amount of mRNA of prostaglandin E 2 -receptor subtypes as compared with normal glomeruli. AE1-329 was administered s.c. at 100 µg/ kg per day for 3 weeks. AE1-329 suppressed the increase in creatinine and cholesterol compared to those in the control nephritic mice. AE1-329-treated nephritic mice had less crescentic glomeruli and less deposition of rabbit IgG (anti-glomerular basement membrane antibody) in glomeruli than the control mice. AE1-329 prevented the development of glomerulonephritis. These findings suggest that EP 4 -receptor agonists are a promising drug to prevent the development of glomerulonephritis.

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“…Activation of the EP1 receptor in kidney tubule cells increases the concentration of intracellular calcium, phosphoinositol turnover, and PKC activity (3,4). EP2 and EP4 receptors are coupled through G s (1) to increase intracellular cAMP in a number of preparations (5)(6)(7)(8). The EP3 receptor undergoes post-transcriptional RNA splicing to produce multiple EP3 isoforms, and activation of these splice variants can increase calcium mobilization or either stimulate or inhibit cAMP production (9 -11).…”

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confidence: 99%

Prostaglandin Receptor Subtypes, EP3C and EP4, Mediate the Prostaglandin E2-induced cAMP Production and Sensitization of Sensory Neurons

Southall¹,

Vasko

2001

Journal of Biological Chemistry

168

150

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Although a number of prostaglandin E 2 (PGE 2 ) receptor subtypes have been cloned, limited studies have been performed to elucidate subtypes that subserve specific actions of this eicosanoid, in part because of a paucity of selective receptor antagonists. Using reverse transcription-polymerase chain reaction (PCR) and antisense oligonucleotides, we examined which prostaglandin E 2 receptor (EP receptor) subtypes are expressed in sensory neurons and which mediate the PGE 2 -induced increase in cAMP production and augmentation of peptide release. Reverse transcription-PCR of cDNA isolated from rat sensory neurons grown in culture revealed PCR products for the EP1, EP2, EP3C, and EP4 receptor subtypes but not the EP3A or EP3B. Preexposing neuronal cultures for 48 h to antisense oligonucleotides of EP3C and EP4 mRNA diminished expression of the respective receptors by ϳ80%, abolished the PGE 2 -stimulated production of cAMP, and blocked the ability of PGE 2 to augment release of immunoreactive substance P and calcitonin gene-related peptide. Pretreating with individual antisense against the EP2, EP3C, or EP4 receptors or combinations of missense oligonucleotides had no effect on PGE 2 -induced activity. Treatment with antisense to EP3C and EP4 receptor subtypes did not alter the ability of forskolin to increase cAMP or enhance peptide release. These results demonstrate that sensory neurons are capable of expressing multiple EP receptor subtypes but that only the EP3C and EP4 receptors mediate PGE 2 -induced sensitization of sensory neurons. Prostaglandin E 2 receptors (EP receptors)1 have been classified into four general subtypes, EP1, EP2, EP3, and EP4, based on cloning and pharmacological manipulations (1, 2). These receptors are G-protein-coupled, and binding of agonists results in activation of various transduction cascades depending on the receptor subtype activated and the cells being studied. Activation of the EP1 receptor in kidney tubule cells increases the concentration of intracellular calcium, phosphoinositol turnover, and PKC activity (3, 4). EP2 and EP4 receptors are coupled through G s (1) to increase intracellular cAMP in a number of preparations (5-8). The EP3 receptor undergoes post-transcriptional RNA splicing to produce multiple EP3 isoforms, and activation of these splice variants can increase calcium mobilization or either stimulate or inhibit cAMP production (9 -11). Because subtypes of the EP receptor can be linked to different transduction cascades in different types of cells, it is critical to determine which receptors and receptorassociated signal transduction pathways are responsible for specific physiological actions of E-series prostaglandins.Although PGE 2 has a number of diverse physiological actions (12), its role in pain and inflammation is of primary importance. Indeed, both the analgesic and the anti-inflammatory actions of the nonsteroidal anti-inflammatory drugs are attributed to their ability to inhibit prostaglandin synthesis (13). In addition, PGE 2 is produced at sites of ...

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Molecular Cloning and Expression of a Rat Prostaglandin E2 Receptor of the EP2 Subtype

Cited by 70 publications

References 16 publications

Involvement of Prostaglandin E2 in Clearance of Aggregated Protein via Protein Kinase A in Glomeruli

Involvement of Prostaglandin E2 in Clearance of Aggregated Protein via Protein Kinase A in Glomeruli

Protective Effect of Prostaglandin EP4-Receptor Agonist on Anti-glomerular Basement Membrane Antibody-Associated Nephritis

Prostaglandin Receptor Subtypes, EP3C and EP4, Mediate the Prostaglandin E2-induced cAMP Production and Sensitization of Sensory Neurons

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