Prostaglandin EP Receptors Involved in Modulating Gastrointestinal Mucosal Integrity

Takeuchi, Koji; Kato, Shinichi; Amagase, Kikuko

doi:10.1254/jphs.10r06cr

Cited by 60 publications

(55 citation statements)

References 92 publications

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“…Mucin secretion. PGE 2 increases gastric mucin secretion and suppression of motor action, and these activities are quite effective in the prevention of gastric mucosal injury (Takeuchi et al, 2010a). It has been reported that EP4 activation promotes mucin secretion from gastric epithelial cells .…”

Section: Other Immune Cellsmentioning

confidence: 99%

“…NSAIDs have been widely used to achieve analgesic and anti-inflammatory effects, but a major limitation to their use is their potential to cause damage to the gastrointestinal mucosa (Levi et al, 1990;Tanaka et al, 2002). The healingimpairing effect of the NSAIDs is due to their inhibition of COX, especially COX-2 Takeuchi et al, 2010a). EP4 activation has been found to attenuate indomethacin-induced intestinal ulcers in rats (Kunikata et al, 2002;Hatazawa et al, 2006;Takeuchi et al, 2010b).…”

Section: Other Immune Cellsmentioning

confidence: 99%

“…PGE 2 increases HCO 3 2 secretion from the rat duodenal mucosa (Takeuchi et al, 1997). It has been suggested that EP4 synergizes with EP3 to promote duodenal mucosal HCO 3 2 secretion (Takeuchi et al, 2010a). Studies have demonstrated that duodenal HCO 3 2 secretion is stimulated by the EP4 agonist ONO-AE1-329 under HCl-induced mucosal acidification conditions (Aoi et al, 2004;Aihara et al, 2007).…”

Section: Other Immune Cellsmentioning

confidence: 99%

See 2 more Smart Citations

The Prostanoid EP4 Receptor and Its Signaling Pathway

Yokoyama

Iwatsubo²,

Umemura³

et al. 2013

Pharmacol Rev

223

257

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Section: Other Immune Cellsmentioning

confidence: 99%

Section: Other Immune Cellsmentioning

confidence: 99%

Section: Other Immune Cellsmentioning

confidence: 99%

See 1 more Smart Citation

The Prostanoid EP4 Receptor and Its Signaling Pathway

Yokoyama

Iwatsubo²,

Umemura³

et al. 2013

Pharmacol Rev

223

257

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“…Upper gastrointestinal (GI) damage is a major adverse effect of NSAID use (16), and, moreover, recent evidence suggests that NSAIDs are responsible for mucosal injury, not only in the upper, but also the lower GI tract (10,16). Prostaglandin synthesis is considered to play a pivotal role in the mechanism of NSAID-induced GI damage (21); however, its pathophysiology still remains to be elucidated.…”

mentioning

confidence: 99%

Expression ofRegfamily genes in the gastrointestinal tract of mice treated with indomethacin

Sun

Fukui

Hara

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Regenerating gene (Reg) family proteins, which are classified into four types, commonly act as trophic and/or antiapoptotic factors in gastrointestinal (GI) diseases. However, it remains unclear how these proteins coordinate their similar roles under such pathophysiological conditions. Here, we investigated the interrelationships of Reg family gene expression with mucosal cell proliferation and apoptosis in nonsteroidal anti-inflammatory drug (NSAID)-induced GI injury. GI injury was induced by subcutaneous injection of indomethacin into Reg I knockout (KO) and wild-type (WT) mice, and its severity was scored histopathologically. Temporal changes in the expression of Reg family genes, mucosal proliferation, and apoptosis were evaluated throughout the GI tract by real-time RT-PCR, Ki-67 immunoreactivity, and TUNEL assay, respectively. Reg I, Reg III family, and Reg IV were predominantly expressed in the upper, middle, and lower GI mucosa, respectively. Expression of Reg I and Reg III family genes was upregulated in specific portions of the GI tract after indomethacin treatment. Ki-67-positive epithelial cells were significantly decreased in the gastric and small-intestinal mucosa of Reg I KO mice under normal conditions. After treatment with indomethacin, the number of TUNEL-positive cells was significantly greater throughout the GI mucosa in Reg I KO mice than in WT mice. Expression of Reg I was independent of that of other Reg family genes in, not only normal GI tissues, but also indomethacin-induced GI lesions. Members of the Reg gene family show distinct profiles of expression in the GI tract, and Reg I independently plays a role in protecting the GI mucosa against NSAID-induced injury.Reg; nonsteroidal anti-inflammatory drug; proliferation; apoptosis; gastrointestinal mucosa NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) are commonly prescribed worldwide for patients with arthritis or cardiac and cerebrovascular diseases (16). Upper gastrointestinal (GI) damage is a major adverse effect of NSAID use (16), and, moreover, recent evidence suggests that NSAIDs are responsible for mucosal injury, not only in the upper, but also the lower GI tract (10, 16). Prostaglandin synthesis is considered to play a pivotal role in the mechanism of NSAID-induced GI damage (21); however, its pathophysiology still remains to be elucidated.The regenerating gene (Reg) was originally isolated from rat regenerating pancreatic islet cells, and its human homolog was named REG I␣ (23). Recently, many Reg-related genes have been isolated and shown to constitute a multigene family (types I-IV) (8). We have previously reported that REG I␣ and REG IV are involved in the pathophysiology of GI inflammation (5, 17) and that, moreover, they act as trophic and/or antiapoptotic factors under inflammatory conditions (17, 18). Other investigators have reported that Reg III family genes are overexpressed in inflamed GI mucosa (11,13) and that their products, including REG I␣ and REG IV proteins, may exert trophic and/or antiapoptotic effects on panc...

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“…The protective effect of PG primarily results from an increase in the secretion of HCO 3 -and mucus, which is realized through PG E 1 and PG E 4 receptors [14]. PG receptors on chief cells of the gastric glands probably play a role in the activation of pepsinogen secretion [9].…”

Section: Resultsmentioning

confidence: 99%

Effect of Proton Pump Inhibitors on the Secretion of Bicarbonates and Pepsinogen Induced by Chemical Stimulation of the Gastric Mucosa

Золотарев

Khropycheva

2013

Bull Exp Biol Med

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Proton pump inhibitors were shown to affect the sensitivity of the gastric mucosa to chemical agents. This effect is associated with inhibition of proton back-diffusion and increase in the permeability of the gastric epithelium. We studied the effect of omeprazole on gastric secretion of bicarbonates and pepsinogen induced by irritation of the gastric mucosa in narcotized rats with a hypertonic solution of high acidity (500 mM NaCl, pH 2.0). Irritation of the gastric mucosa increased the basal secretion of bicarbonates and potentiated the secretion of HCO3(-)and pepsinogen induced by electrostimulation of the vagus nerve. Omeprazole stimulated the prostaglandin-induced increase in the basal secretion of HCO3(-)and pepsinogen. By contrast, bicarbonate production in response to vagal stimulation was suppressed in the presence of omeprazole. Our results indicate that proton pump blockade has a modulatory effect on gastric secretion of bicarbonates and pepsinogen induced by chemical stimulation of the gastric mucosa.

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Prostaglandin EP Receptors Involved in Modulating Gastrointestinal Mucosal Integrity

Cited by 60 publications

References 92 publications

The Prostanoid EP4 Receptor and Its Signaling Pathway

The Prostanoid EP4 Receptor and Its Signaling Pathway

Expression ofRegfamily genes in the gastrointestinal tract of mice treated with indomethacin

Effect of Proton Pump Inhibitors on the Secretion of Bicarbonates and Pepsinogen Induced by Chemical Stimulation of the Gastric Mucosa

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