Energy requirements of glutamatergic pathways in rabbit retina.
In vitro rabbit retina was used as an example of CNS tissue in experiments designed to measure the energy requirements associated with the activation of different types of glutamate receptors. Retinas were exposed to glutamate and to four analogs: kainate, 2-amino-4-phosphonobutyric acid (APB), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 2-amino-5-phosphonovaleric acid (APV). The changes in O2 consumption and lactate production were determined using a recently developed experimental system that permitted simultaneous measurements of the rates at which O2 was removed from the medium and acid was added. The glutamatergic agents had relatively little effect on oxidative metabolism, but they caused large changes in glycolysis. Kainate increased retinal lactate production by 50%, whereas APB, CNQX, and APV reduced it by 23%, 19%, and 35%, respectively. Glutamate increased lactate production by 16% when administered after APB, but decreased it by 12% when administered after CNQX. The changes in energy metabolism coincided with changes in electrophysiological function. Since the energy metabolism of many retinal cells was presumably not much affected by the glutamatergic agents, the changes measured as a percent of total retinal glycolysis must have reflected considerably larger fractional changes in the cells most affected. From the response to inhibitors, it seems probable that even under resting conditions in darkness, activity in glutamatergic pathways is responsible for more than 50% of the glycolytically derived energy used by the cells involved. It also seems probable (particularly from the response to kainate) that under some circumstances the cells' energy metabolism and/or transport capability cannot meet the requirements imposed by glutamate-induced increases in function.(ABSTRACT TRUNCATED AT 250 WORDS)
Ames
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Neurosurgical Service, Massachusetts General Hospital, Boston 02114.
Li
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects / Q000528:radiation effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005973:Glutamine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007608:Kainic Acid / Q000494:pharmacology; D008027:Light; D010101:Oxygen Consumption / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D012160:Retina / Q000378:metabolism*
D000613:Aminobutyrates; D005971:Glutamates; D011810:Quinoxalines; D005973:Glutamine; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C012729:2-amino-4-phosphonobutyric acid; D007608:Kainic Acid