Role of Prostanoid Production and Receptors in the Regulation of Retinal Endogenous Amino Acid Neurotransmitters by 8-Isoprostaglandin E₂, Ex Vivo

摘要

The role of enzymes and receptors of the prostanoid pathway in the inhibitory effect of 8-isoprostaglandin E₂ (8-isoPGE₂) on endogenous amino acid neurotransmitter levels was examined, ex vivo. Freshly isolated bovine eyeballs were injected intravitreally with IsoPs, incubated in Krebs buffer for 30 min and retina prepared for HPLC-ECD detection of amino acids. 8-isoPGE₂ attenuated retinal glutamate and its metabolite, glutamine and glycine in a concentration-dependent manner. The non-selective cyclooxygenase (COX)-inhibitor, flurbiprofen, COX-2 selective inhibitor, NS-398 and thromboxane (Tx) synthase inhibitor, furegrelate had no effect on both basal amino acid levels and the inhibitory effects of 8-isoPGE₂ (1–100 μM) on the retinal amino acids. Whereas the TP-receptor antagonist SQ-29548(10 μM) exhibited no effect, SC-19220(EP₁; 30 μM), AH-6809(EP_1–3; 30 μM) and AH-23848(EP₄; 30 μM) reversed the inhibitory effects of 8-isoPGE₂ (0.01–100 μM) on glutamate, glutamine and glycine levels. We conclude that prostanoid EP-receptors regulate the inhibitory effect of 8-isoPGE₂ on basal levels of endogenous amino acids in bovine retina, ex vivo.