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Abstract #24201 Published in IGR 11-3

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

Mori A; Ishii T; Kuroki T; Shigeta N; Sakamoto K; Nakahara T; Ishii K
European Journal of Pharmacology 2009; 616: 64-67

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Prostaglandin E₂ (PGE₂) plays an important role in promoting inflammation and neurological disorders. The actions of PGEE₂ are mediated by four different G-protein-coupled receptors (EP₁, EP₂, EP₃, and EP₄). The purpose of this study was to determine whether stimulation of prostanoid EP₂ 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 E₂ (ONO-AE1-259-01), a selective prostanoid EP₂ 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 EP₂ receptor may be a target for neuroprotective intervention in the retinal diseases associated with glutamate-induced excitotoxicity, such as glaucoma and diabetic retinopathy.

Dr. T. Nakahara, Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. nakaharat@pharm.kitasato-u.ac.jp

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Classification:

11.8 Neuroprotection (Part of: 11 Medical treatment)
11.4 Prostaglandins (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)

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