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(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.
Mori
Asami
A
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Tokyo, Japan.
Ishii
Takayuki
T
Kuroki
Taiyo
T
Shigeta
Naoki
N
Sakamoto
Kenji
K
Nakahara
Tsutomu
T
Ishii
Kunio
K
D000818:Animals; D002452:Cell Count; D015232:Dinoprostone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D007267:Injections; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012162:Retinal Degeneration / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology
C544312:11,15-O-dimethylprostaglandin E2; D009498:Neurotoxins; C545646:Ptger2 protein, rat; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D018698:Glutamic Acid; D016202:N-Methylaspartate; D015232:Dinoprostone