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

The pharmacological basis of glutamate-induced [H-3]D-aspartate release was investigated in isolated human, bovine and rabbit retinas. Isolated mammal ian retinas were preloaded with [H-3]D-aspartate and then prepared for stud ies of neurotransmitter release using the superfusion method. Release of [H -3]D-aspartate was elicited by K+ (50 mM) or by L-glutamate. In bovine reti nas, L-glutamate, but not D-glutamate induced an overflow of [H-3]D-asparta te that was partially inhibited by low external calcium, omega-conotoxin (1 0 nM) or nitrendipine (1 mu M). Metabotropic glutamate receptor (GLUR) agon ists also evoked [H-3]D-aspartate release in both bovine and human retinas whereas polyamines only enhanced the excitatory effects of L-glutamate on [ H-3]D-aspartate release. Antagonists of GLURs and the polyamine site inhibi ted L-glutamate evoked [H-3]D-aspartate overflow with the following rank or der of potency: MCPG >ifenprodil > AP-5 > arcaine> MK-801. In conclusion, L -glutamate-induces a stereoselective, calcium-dependent release of [H-3]D-a spartate from isolated mammalian retinas that can be mimicked by GLUR agoni sts (and blocked by both receptor and polyamine site antagonists).