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, omega-conotoxin (10 nM) or nitrendipine (1 microM). 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).
Ohia
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Department of Pharmaceutical and Administrative Sciences, School of Pharmacy and Allied Health Profession, Creighton University, Omaha, NE 68178, USA. seohia@creighton.edu
Opere
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Awe
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Adams
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Sharif
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D000328:Adult; D000368:Aged; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002417:Cattle; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D011817:Rabbits; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid