The prostanoid EP(2) receptor agonist ONO-AE1-259-01 protects against glutamate-induced neurotoxicity in rat retina

Prostaglandin E(2) (PGE(2)) plays an important role in promoting inflammation and neurological disorders. The actions of PGE(2) are mediated by four different G-protein-coupled receptors (EP(1), EP(2), EP(3), and EP(4)). The purpose of this study was to determine whether stimulation of prostanoid EP...

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Bibliographic Details
Published in:European journal of pharmacology 2009-08, Vol.616 (1-3), p.64
Main Authors: Mori, Asami, Ishii, Takayuki, Kuroki, Taiyo, Shigeta, Naoki, Sakamoto, Kenji, Nakahara, Tsutomu, Ishii, Kunio
Format: Article
Language:English
Subjects:
Animals
Cell Count
Dinoprostone - administration & dosage
Dinoprostone - analogs & derivatives
Dinoprostone - pharmacology
Glutamic Acid - toxicity
Injections
Male
N-Methylaspartate - pharmacology
Neurotoxins - toxicity
Rats
Rats, Sprague-Dawley
Receptors, Prostaglandin E - agonists
Receptors, Prostaglandin E, EP2 Subtype
Retina - drug effects
Retina - pathology
Retinal Degeneration - pathology
Retinal Ganglion Cells - drug effects
Retinal Ganglion Cells - pathology
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Summary:Prostaglandin E(2) (PGE(2)) plays an important role in promoting inflammation and neurological disorders. The actions of PGE(2) are mediated by four different G-protein-coupled receptors (EP(1), EP(2), EP(3), and EP(4)). The purpose of this study was to determine whether stimulation of prostanoid EP(2) receptors has the potential to prevent the excitotoxic injuries in the retina. For this purpose, we examined the effect of 11,15-O-dimethyl prostaglandin E(2) (ONO-AE1-259-01), a selective prostanoid EP(2) receptor agonist, on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina. ONO-AE1-259-01 (2 or 20 nmol) together with NMDA (200 nmol) was given intravitreally, and histological evaluation was performed at 1 week after the injection. ONO-AE1-259-01 concentration-dependently prevented NMDA-induced cell loss in ganglion cell layer and reduction in thickness of inner plexiform layer. These results indicate that ONO-AE1-259-01 protects the excitotoxic injuries in the rat retina, and that the prostanoid EP(2) receptor may be a target for neuroprotective intervention in the retinal diseases associated with glutamate-induced excitotoxicity, such as glaucoma and diabetic retinopathy.
ISSN:1879-0712
DOI:10.1016/j.ejphar.2009.04.051