Gastrointestinal Protective Action of Prostaglandin E2 and EP Receptor Subtypes

2002 ◽  
pp. 227-242 ◽  
Author(s):  
K. Takeuchi ◽  
S. Kato ◽  
A. Tanaka
Keyword(s):  
Protective Action ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Ep Receptor

Prostaglandin E prevents indomethacin-induced gastric and intestinal damage through different EP receptor subtypes

2001 ◽  
Vol 95 (1-6) ◽  
pp. 157-163 ◽  
Author(s):  
Tomonori Kunikata ◽  
Hideo Araki ◽  
Mosanori Takeeda ◽  
Shinichi Kato ◽  
Koji Takeuchi
Keyword(s):  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Intestinal Damage ◽  
Ep Receptor

scholarly journals Renal prostaglandin E2 receptor (EP) expression profile is altered in streptozotocin and B6-Ins2Akita type I diabetic mice

2007 ◽  
Vol 292 (1) ◽  
pp. F278-F284 ◽  
Author(s):  
Rania Nasrallah ◽  
Huaqi Xiong ◽  
Richard L. Hébert
Keyword(s):  
Expression Profile ◽  
Receptor Expression ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Type I ◽  
Diabetic Mice ◽  
Diabetic Kidney ◽  
Urine Albumin ◽  
Ep Receptor ◽  
Prostaglandin E2 Receptor

The homeostatic function of prostaglandin E2 (PGE2) is dependent on a balance of EP receptor-mediated events. A disruption in this balance may contribute to the progression of renal injury. Although PGE2 excretion is elevated in diabetes, the expression of specific EP receptor subtypes has not been studied in the diabetic kidney. Therefore, the purpose of this study was to characterize the expression profile of four EP receptor subtypes (EP1-4) in 16-wk streptozotocin (STZ) and B6-Ins2Akita type I diabetic mice. In diabetic mice, the ratio of kidney weight to body weight was increased twofold compared with controls, blood glucose was elevated, but urine albumin was only increased in B6-Ins2Akita mice. The excretion of PGE2 and its metabolite was augmented two- to fourfold as determined by enzyme immunoassay. Accordingly, renal cyclooxygenases were also increased in diabetic mice, with isoform-specific and regional differences in each model. Finally, there was altered EP1-4 receptor expression in diabetic kidneys, with significant differences between STZ and B6-Ins2Akita mice (fold-control). In STZ mice, cortical EP1 increased by 1.6, EP3 increased by 2.3, and EP4 decreased by 0.63; yet in B6-Ins2Akita mice, cortical EP1 increased by 2.4, but there was a general decrease in the remaining subtypes. Similarly, in the STZ medulla EP3 increased by 3.6, but both EP1 and EP3 increased by 5.5 and 1.95, respectively, in B6-Ins2Akita mice. Therefore, knowing the pattern of change in relative EP receptor expression in the kidney could be useful in identifying specific EP targets for the prevention of various components of diabetic kidney disease.

scholarly journals PGE2-mediated cytoprotection in renal epithelial cells: evidence for a pharmacologically distinct receptor

1997 ◽  
Vol 273 (4) ◽  
pp. F507-F515 ◽  
Author(s):  
Thomas J. Weber ◽  
Terrence J. Monks ◽  
Serrine S. Lau
Keyword(s):  
Molecular Mechanisms ◽  
Cellular Level ◽  
Binding Activity ◽  
Epithelial Cell Line ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Kinase C ◽  
Toxic Concentration ◽  
Ep Receptor ◽  
Responsive Element

Although the exact mechanism of prostaglandin E2(PGE2)-mediated cytoprotection has not been elucidated, its ability to induce cytoprotection in cell culture suggests this action occurs at the cellular level. The present studies were conducted to determine whether PGE2induces protection against 2,3,5-(trisglutathion- S-yl)-hydroquinone [2,3,5-(trisglutathion- S-yl)-HQ]-mediated cytotoxicity in a renal proximal tubule epithelial cell line (LLC-PK1) and to delineate the cellular and molecular mechanisms associated with this response. Pretreatment of LLC-PK1cells with 0.01–40 μM PGE2for 24 h fully protects against a moderately toxic concentration of 2,3,5-(trisglutathion- S-yl)-HQ. PGE2-mediated cytoprotection is observed in cells pretreated at pH 7.4 but not at pH 7.8. However, cytoprotection is observed in LLC-PK1cells pretreated with the PGE2analog, 11-deoxy-16,16-dimethyl PGE2(DDM-PGE2) but not with the PGE2receptor [E-prostanoid (EP)] agonists 17-phenyltrinor PGE2(EP1), 11-deoxy PGE1(EP2/EP4), sulprostone (EP1/EP3), PGE1, or PGA2. 12- O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of protein kinase C (PKC), also induces cytoprotection, supporting a role for this pathway in the cytoprotective response. PGE2, DDM-PGE2, and TPA all induce the binding of nuclear proteins to a TPA responsive element (TRE), whereas analogs that did not induce cytoprotection (PGE1, 17-phenyltrinor PGE2, sulprostone) were without effect. DDM-PGE2- and TPA-mediated cytoprotection and TRE binding activity are inhibited by N-(2{[3-(4-bromophenyl)-2-propenyl]-amino}-ethyl)-5-isoquinolinesulfonamide (H-89), a PKC inhibitor. These data suggest that cytoprotection by PGE2and DDM-PGE2in LLC-PK1cells is mediated by a PKC-coupled receptor, which is pharmacologically distinct from the presently classified EP receptor subtypes.

Differential localization of prostaglandin E receptor subtypes in human kidney

1996 ◽  
Vol 270 (5) ◽  
pp. F912-F918 ◽  
Author(s):  
M. D. Breyer ◽  
L. Davis ◽  
H. R. Jacobson ◽  
R. M. Breyer
Keyword(s):  
In Situ Hybridization ◽  
Collecting Duct ◽  
Human Kidney ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Ep Receptors ◽  
Inner Medullary Collecting Duct ◽  
Ep Receptor ◽  
Medullary Collecting Duct

Four prostaglandin E2 (PGE2) receptors designated EP1, EP2, EP3, and EP4 have been pharmacologically identified, cloned, and sequenced. The present studies determined the intrarenal distribution of these EP-receptor subtypes in human kidney using in situ hybridization with riboprobes for the human EP receptors. mRNA for the phosphatidylinositol hydrolysis-coupled EP receptor was highly expressed in cortical, outer medullary, and inner medullary collecting duct. RNA for the Gi-coupled EP3 receptor was primarily expressed in the cortical and outer medullary collecting duct, as well as in the medullary thick ascending limb; however, it was absent from the inner medullary collecting duct. Expression of mRNA for EP1 and EP3 in connecting segment could not be excluded. There was no expression of the GS-coupled EP2 receptor mRNA detected in human kidney by in situ hybridization; however, mRNA for the GS-coupled EP4 receptor was highly expressed in the glomerulus. These studies demonstrate distinct regions of intrarenal expression for the different EP receptors and suggest that each receptor subtype may modulate different aspects of renal function in humans.

scholarly journals Gastrointestinal cytoprotection by prostaglandin E and EP receptor subtypes

2001 ◽  
Vol 117 (4) ◽  
pp. 274-282 ◽  
Author(s):  
Koji TAKEUCHI ◽  
Shinichi KATO ◽  
Akiko TANAKA
Keyword(s):  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Ep Receptor

Functional and molecular aspects of prostaglandin E receptors in the cortical collecting duct

1995 ◽  
Vol 73 (2) ◽  
pp. 172-179 ◽  
Author(s):  
Richard L. Hébert ◽  
Richard M. Breyer ◽  
Harry R. Jacobson ◽  
Matthew D. Breyer
Keyword(s):  
In Situ Hybridization ◽  
Cyclic Amp ◽  
Water Transport ◽  
Collecting Duct ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Cortical Collecting Duct ◽  
Endogenous Prostaglandin ◽  
Ep Receptor

Endogenous prostaglandin (PG) E2 production potently modulates salt and water transport in the kidney. Multiple direct effects of PGE2 on epithelial water and sodium transport have been demonstrated in the rabbit cortical collecting duct (CCD). Both functional and molecular studies now suggest that these disparate effects of PGE2 on CCD function are mediated by different EP receptors. When added in the presence of vasopressin, PGE2 inhibits cyclic AMP generation and water absorption. These effects are mediated via an inhibitory G-protein (Gi). In situ hybridization demonstrates high levels of expression of the Gi-coupled EP3 receptor in the rabbit collecting duct. However, by itself, PGE2 also stimulates cyclic AMP generation and water permeability. These effects appear to be mediated via a distinct EP receptor (possibly an EP4 receptor). PGE2 also increases intracellular Ca2+ in the CCD and inhibits Na+ absorption via a Ca2+-dependent mechanism. The EP1 receptor is postulated to be responsible for this action of PGE2. We suggest receptor-selective prostaglandin analogs may be used to selectively modulate sodium and water transport in the kidney.Key words: EP receptor subtypes, G-proteins, in situ hybridization, prostaglandin E2, phosphatidylinositol biphosphate hydrolysis.

Dual action of prostaglandin E2 on gastric acid secretion through different EP-receptor subtypes in the rat

2005 ◽  
Vol 289 (1) ◽  
pp. G64-G69 ◽  
Author(s):  
Shinichi Kato ◽  
Eitaro Aihara ◽  
Katsuhide Yoshii ◽  
Koji Takeuchi
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Ep Receptor ◽  
Dual Action ◽  
Secretion Inhibition

We examined the role of prostaglandin E (EP) receptor subtypes in the regulation of gastric acid secretion in the rat. Under urethane anesthesia, the stomach was superfused with saline, and the acid secretion was determined at pH 7.0 by adding 50 mM NaOH. The acid secretion was stimulated by intravenous infusion of histamine or pentagastrin. Various EP agonists were administered intravenously, whereas EP antagonists were given subcutaneously 30 min or intravenously 10 min before EP agonists. PGE2 suppressed the acid secretion stimulated by either histamine or pentagastrin in a dose-dependent manner. The acid inhibitory effect of PGE2 was mimicked by sulprostone (EP1/EP3 agonist) but not butaprost (EP2 agonist) or AE1–329 (EP4 agonist). The inhibitory effect of sulprostone, which was not affected by ONO-8711 (EP1 antagonist), was more potent against pentagastrin- (50% inhibition dose: 3.6 μg/kg) than histamine-stimulated acid secretion (50% inhibition dose: 18.0 μg/kg). Pentagastrin increased the luminal release of histamine, and this response was also inhibited by sulprostone. On the other hand, AE1–329 (EP4 agonist) stimulated the acid secretion in vagotomized animals with a significant increase in luminal histamine. This effect of AE1–329 was totally abolished by cimetidine as well as AE3–208 (EP4 antagonist). These results suggest that PGE2 has a dual effect on acid secretion: inhibition mediated by EP3 receptors and stimulation through EP4 receptors. The former effect may be brought about by suppression at both parietal and enterochromaffin-like cells, whereas the latter effect may be mediated by histamine released from enterochromaffin-like cells.

Prostaglandin E (EP) receptor subtypes and sleep

Neuroreport ◽  
2000 ◽  
Vol 11 (10) ◽  
pp. 2127-2131 ◽  
Author(s):  
Yasushi Yoshida ◽  
Hitoshi Matsumura ◽  
Tomoko Nakajima ◽  
Masaharu Mandai ◽  
Takahito Urakami ◽  
...  
Keyword(s):  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Ep Receptor

scholarly journals Sensitization of TRPV1 by EP1 and IP Reveals Peripheral Nociceptive Mechanism of Prostaglandins

2005 ◽  
Vol 1 ◽  
pp. 1744-8069-1-3 ◽  
Author(s):  
Tomoko Moriyama ◽  
Tomohiro Higashi ◽  
Kazuya Togashi ◽  
Tohko Iida ◽  
Eri Segi ◽  
...  
Keyword(s):  
Thermal Hyperalgesia ◽  
Hek293 Cells ◽  
Prostaglandin E ◽  
Temperature Threshold ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Cellular Mechanisms ◽  
Nociceptive Responses ◽  
Ep Receptor ◽  
Deficient Mice

Prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) are major inflammatory mediators that play important roles in pain sensation and hyperalgesia. The role of their receptors (EP and IP, respectively) in inflammation has been well documented, although the EP receptor subtypes involved in this process and the underlying cellular mechanisms remain to be elucidated. The capsaicin receptor TRPV1 is a nonselective cation channel expressed in sensory neurons and activated by various noxious stimuli. TRPV1 has been reported to be critical for inflammatory pain mediated through PKA- and PKC-dependent pathways. PGE2 or PGI2increased or sensitized TRPV1 responses through EP1 or IP receptors, respectively predominantly in a PKC-dependent manner in both HEK293 cells expressing TRPV1 and mouse DRG neurons. In the presence of PGE2 or PGI2, the temperature threshold for TRPV1 activation was reduced below 35°C, so that temperatures near body temperature are sufficient to activate TRPV1. A PKA-dependent pathway was also involved in the potentiation of TRPV1 through EP4 and IP receptors upon exposure to PGE2 and PGI2, respectively. Both PGE2-induced thermal hyperalgesia and inflammatory nociceptive responses were diminished in TRPV1-deficient mice and EP1-deficient mice. IP receptor involvement was also demonstrated using TRPV1-deficient mice and IP-deficient mice. Thus, the potentiation or sensitization of TRPV1 activity through EP1 or IP activation might be one important mechanism underlying the peripheral nociceptive actions of PGE2 or PGI2.

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