Gastric Cytoprotection by Prostaglandin E2 — Relation to EP Receptor Subtypes —

2002 ◽  
pp. 169-180
Author(s):  
Koji Takeuchi ◽  
Shinichi Kato ◽  
Yusaku Komoike ◽  
Yoshihiro Ogawa ◽  
Masanori Takeeda
Keyword(s):  
Prostaglandin E2 ◽  
Receptor Subtypes ◽  
Gastric Cytoprotection ◽  
Ep Receptor

scholarly journals Molecular mechanisms underlying prostaglandin E2-exacerbated inflammation and immune diseases

2019 ◽  
Vol 31 (9) ◽  
pp. 597-606 ◽  
Author(s):  
Kyoshiro Tsuge ◽  
Tomoaki Inazumi ◽  
Akira Shimamoto ◽  
Yukihiko Sugimoto
Keyword(s):  
Autoimmune Diseases ◽  
Prostaglandin E2 ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Mast Cell Activation ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Ep Receptor ◽  
Anti Inflammatory

Abstract Prostaglandins (PGs) are the major lipid mediators in animals and which are biosynthesized from arachidonic acid by the cyclooxygenases (COX-1 or COX-2) as the rate-limiting enzymes. Prostaglandin E2 (PGE2), which is the most abundantly detected PG in various tissues, exerts versatile physiological and pathological actions via four receptor subtypes (EP1–4). Non-steroidal anti-inflammatory drugs, such as aspirin and indomethacin, exert potent anti-inflammatory actions by the inhibition of COX activity and the resulting suppression of PG production. Therefore, PGE2 has been shown to exacerbate several inflammatory responses and immune diseases. Recently, studies using mice deficient in each PG receptor subtype have clarified the detailed mechanisms underlying PGE2-associated inflammation and autoimmune diseases involving each EP receptor. Here, we review the recent advances in our understanding of the roles of PGE2 receptors in the progression of acute and chronic inflammation and autoimmune diseases. PGE2 induces acute inflammation through mast cell activation via the EP3 receptor. PGE2 also induces chronic inflammation and various autoimmune diseases through T helper 1 (Th1)-cell differentiation, Th17-cell proliferation and IL-22 production from Th22 cells via the EP2 and EP4 receptors. The possibility of EP receptor-targeted drug development for the treatment of immune diseases is also discussed.

Prostaglandin EP receptor subtypes and gastric cytoprotection

2002 ◽  
Vol 10 (4-6) ◽  
pp. 303-312 ◽  
Author(s):  
Koji Takeuchi ◽  
Shoko Hase ◽  
Masanori Takeeda ◽  
Masato Nakashima ◽  
Aya Yokota
Keyword(s):  
Receptor Subtypes ◽  
Gastric Cytoprotection ◽  
Ep Receptor

scholarly journals Characterization of EP receptor subtypes responsible for prostaglandin E2 -induced pain responses by use of EP1 and EP3 receptor knockout mice

2001 ◽  
Vol 133 (3) ◽  
pp. 438-444 ◽  
Author(s):  
Toshiaki Minami ◽  
Hiroyuki Nakano ◽  
Takuya Kobayashi ◽  
Yukihiko Sugimoto ◽  
Fumitaka Ushikubi ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Knockout Mice ◽  
Receptor Subtypes ◽  
Ep Receptor ◽  
Ep3 Receptor ◽  
Pain Responses

scholarly journals Characterization of EP-receptor subtypes involved in allodynia and hyperalgesia induced by intrathecal administration of prostaglandin E2 to mice

1994 ◽  
Vol 112 (3) ◽  
pp. 735-740 ◽  
Author(s):  
Toshiaki Minami ◽  
Isao Nishihara ◽  
Rumiko Uda ◽  
Seiji Ito ◽  
Masayoshi Hyodo ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Intrathecal Administration ◽  
Receptor Subtypes ◽  
Ep Receptor

Abstract P352: Prostaglandin E2 Reduces Mitochondrial Function in Adult Mouse Cardiomyocytes

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Pamela Harding ◽  
Timothy D Bryson ◽  
Indrani Datta ◽  
Yun Wang ◽  
Albert Levin
Keyword(s):  
Membrane Potential ◽  
Ejection Fraction ◽  
Prostaglandin E2 ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Complex I ◽  
Mitochondrial Membrane ◽  
Receptor Subtypes ◽  
Atp Levels ◽  
Complex I Activity

Hypertension is a leading cause of heart failure and both conditions are characterized by increased prostaglandin E2 (PGE2) which signals through 4 receptor subtypes (EP1-EP4) to elicit diverse physiologic effects. We previously reported that cardiomyocyte-specific deletion of the EP4 receptor results in a phenotype of dilated cardiomyopathy in male mice that is characterized by reduced ejection fraction. Subsequent gene array on left ventricles from these mice, coupled with Ingenuity Pathway Analysis (IPA) demonstrated that genes differentiating WT mice and EP4 KO mice with low ejection fraction were significantly overrepresented in mitochondrial (p=2.51x10 -28 ) and oxidative phosphorylation (p=3.16 x10 -30 ) pathways. We therefore hypothesized that PGE2 could reduce mitochondrial function. To test this hypothesis, we used isolated mouse cardiomyocytes (AVM) from 16-18 week old male C57Bl/6 mice and treated them with 1 μM PGE2 for various times. Mitochondrial gene expression was examined using a RT-profiler kit for mitochondrial energy metabolism, complex I activity with a spectrophotometric assay, ATP levels with a bioluminescence assay and mitochondrial membrane potential using JC-1 staining. Treatment of AVM with PGE2 for 4 hrs reduced expression of multiple genes from mitochondrial pathways including sub units of mitochondrial NADH dehydrogenase ubiquinone flavoprotein (Nduf), a component of complex I. In accord with the mRNA data, Complex I activity was reduced by 50% (p < 0.05) by 4 hr treatment with PGE2, from 1.32 ± 0.36 to 0.66 ± 0.08 mOD/min. Cytochrome c oxidase subunit 8 (Cox8c) mRNA was also reduced from a control value of 1.00 to -1.75 ± 0.20 (p < 0.005) after PGE2 treatment. Immuno-fluorescence showed that JC-1 aggregates were reduced after 1 or 3 hr treatment with either 1 μM PGE2 or the EP3 agonist, sulprostone, suggesting reduced mitochondrial membrane potential. Subsequent experiments also showed that ATP levels were reduced 16% from 11.18 ± 0.71 nmol to 9.39 ± 0.83 nmol after treatment with sulprostone for only 1 hr. Taken together, these results suggest that increased PGE2 in hypertension may contribute to impaired mitochondrial function and provide yet another link between inflammation and cardiac dysfunction.

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