Localization of amino acid neurotransmitters following in vitro ischemia and anoxia in the rat retina.
Glutamate and gamma-aminobutyric acid (GABA) are two of the dominant neurotransmitters in the retina and brain. The production/degradation of glutamate and GABA involves an intricate interrelationship between neurons and glia, as well as aerobic and anaerobic metabolic pathways. The aim of this work was to develop an in vitro model of retinal ischemia/anoxia and determine the changes in cellular localization of glutamate and GABA and the time course for such changes. After anoxic/ischemic insult, glutamate and GABA rapidly accumulate within glia with GABA showing a quicker time course and larger magnitude change. The accumulation time constant for both glutamate and GABA under anoxic conditions was dependent upon glucose concentration: high glucose levels resulted in delayed glial amino acid loading. The differences in time constants between GABA and glutamate glial loading most likely reflect the multitude of glutamate degradation pathways compared to the single aerobically dependent GABA pathway. Oxygen availability and reduced glucose (hypoglycemia) lead to an almost immediate increase (within 1 min) of glutamate and GABA labelling within glia. In addition, altered labelling patterns were found under anoxic/ischemic conditions for amino acids involved in glutamate transamination reactions: aspartate, leucine, alanine. and ornithine. These changes are consistent with alterations of equilibria of enzymatic reactions involved in glutamate metabolism, and thus support a role for all four amino acids in glutamate metabolism within a variety of retinal neurons.
Napper
G A
GA
Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia.
Pianta
M J
MJ
Kalloniatis
M
M
D000596:Amino Acids / Q000378:metabolism*; D000693:Anaerobiosis; D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism; D051381:Rats; D011915:Rats, Inbred BUF; D012016:Reference Values; D012160:Retina / Q000378:metabolism*; D012164:Retinal Diseases / Q000378:metabolism*; D012171:Retinal Vessels; D014018:Tissue Distribution; D000637:Transaminases / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D018377:Neurotransmitter Agents; D011355:Prodrugs; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000637:Transaminases