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M. Zhao, S. E. Ohia, C. A. Opere; Involvement of Prostanoid Receptors in the Regulation of Retinal Endogenous Amino Acid Neurotransmitter Levels by 8-Isoprostaglandin E2 , ex vivo. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2624.
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© ARVO (1962-2015); The Authors (2016-present)
We investigated the role of prostanoid receptors in the inhibitory action of 8-isoPGE2 on endogenous neurotransmitter levels in bovine retina, ex vivo.
Freshly isolated bovine eyeballs were equilibrated in oxygenated Krebs buffer solution before being injected intravitreally with either 8-isoPGE2 or vehicle for control. After 30 minutes of incubation in Krebs buffer solution, the retina was isolated from each eyeball and prepared for measurement of glutamate, glutamine and glycine by HPLC-EC. When used, prostanoid receptor antagonists were injected intravitreally into the eyeballs 15 minutes prior to application of 8-isoPGE2 or PGE2.
Intravitreally injected 8-isoPGE2 (10 nM - 100 µM) caused a concentration-dependent decrease in basal levels of the excitatory amino acid neurotransmitter, glutamate and its metabolite, glutamine and the inhibitory neurotransmitter, glycine in bovine retina, ex vivo yielding IC35 values of 1.5 µM, 5.0 µM and 100 µM, respectively. Similarly, the prostanoid, PGE2 (10 µM) inhibited (p<0.001) endogenous glutamate, glutamine and glycine levels by 48.4%, 45.3% and 29.5%, respectively. The prostanoid receptor antagonists, AH-6809 (EP2/3), AH-23848 (EP4), SC-19220 (EP1) and SQ-29548 (TP) had no effect (p>0.05) on the endogenous levels of glutamate, glutamine, and glycine. AH-6809 (30 µM) and AH-23848 (30 µM) completely reversed, while SC-19220 (30 µM) partially reversed 8-isoPGE2 (1 µM and 100 µM)-induced reduction of basal glutamate, glutamine and glycine levels in bovine retina, ex vivo. In contrast, SQ-29548 (30 µM) had no effect (P>0.05) effect on the isoprostane response. Both SC-19220 (30 µM) and AH-23848 (30 µM) completely reversed the inhibitory effect of PGE2 on basal levels of glutamate, glutamine and glycine.
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