Human, bovine, and rabbit retinal glutamate-induced [³H]D-aspartate release: Role in excitotoxicity

The pharmacological basis of glutamate-induced [³H]D-aspartate release was investigated in isolated human, bovine and rabbit retinas. Isolated mammalian retinas were preloaded with [³H]D-aspartate and then prepared for studies of neurotransmitter release using the superfusion method. Release of [³H]D-aspartate was elicited by K⁺ (50 mM) or by L-glutamate. In bovine retinas, L-glutamate, but not D-glutamate induced an overflow of [³H]D-aspartate that was partially inhibited by low external calcium, ω-conotoxin (10 nM) or nitrendipine (1 μM). Metabotropic glutamate receptor (GLUR) agonists also evoked [³H]D-aspartate release in both bovine and human retinas whereas polyamines only enhanced the excitatory effects of L-glutamate on [³H]D-aspartate release. Antagonists of GLURs and the polyamine site inhibited L-glutamate evoked [³H]D-aspartate overflow with the following rank order of potency: MCPG >ifenprodil > AP-5 > arcaine> MK-801. In conclusion, L-glutamate-induces a stereoselective, calcium-dependent release of [³H]D-aspartate from isolated mammalian retinas that can be mimicked by GLUR agonists (and blocked by both receptor and polyamine site antagonists).