An agonist for the prostaglandin E2 receptor subtype EP4 protects the liver from carbon tetrachloride-induced acute injury

Prostaglandin (PG) E2 exerts its action through the receptor subtype EPs (EP1, EP2, EP3, EP4). We examined the effects of novel EP agonists in acute liver injury. Expressions of mRNAs for EP2, EP3 and EP4 were found in the liver, when examined by RT-PCR. In wild type mice, lactate dehydrogenase (LDH...

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Published in:Journal of Pharmacological Sciences 2004, Vol.94 (suppl.3), p.253-253
Main Authors: Yuji Okada, Koh-ichi Yuhki, Katsura Nakanishi, Yayoi Hosoki, Akiyoshi Hara, Takayuki Fujino, Yutaka Kohgo, Shuh Narumiya, Fumitaka Ushikubi
Format: Article
Language:Japanese
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Summary:Prostaglandin (PG) E2 exerts its action through the receptor subtype EPs (EP1, EP2, EP3, EP4). We examined the effects of novel EP agonists in acute liver injury. Expressions of mRNAs for EP2, EP3 and EP4 were found in the liver, when examined by RT-PCR. In wild type mice, lactate dehydrogenase (LDH) levels in plasma elevated markedly after 24 h of CCl4 administration (80 mg/kg, i. p. ), indicating the induction of acute liver injury. An EP4 agonist ONO-4819 (100 ug/kg, i. p. ) significantly reduced the elevation of LDH level, but EP2- and EP3-specific agonists could not. In addition, ONO-4819 significantly reduced hepatic necrotic area 48 h after CCl4 administration. The hepato-protective action of ONO-4819 was absent, however, in EP4-deficient mice. These results indicate that PGE2 protect the liver from CCl4 induced acute injury via EP4, and suggest that EP4 agonists are useful for treatment of acute liver injury.
ISSN:1347-8613