Glial and neuronal glutamate transport following glutamine synthetase inhibition.
Glutamate transport into striatal tissue preparations was studied following inhibition of glutamine synthetase with methionine sulfoximine (MSO). Glutamate uptake in striatal tissue prisms was elevated for up to 7 days following an intraventricular (i.c.v.) injection of MSO. Kinetic analysis of glutamate uptake revealed that a high- and a low-affinity carrier system mediated the transport of glutamate into tissue slices. MSO altered the transport of glutamate via the high-affinity carrier without changing the characteristics of low-affinity glutamate transport. MSO increased the Km for glutamate and the Vmax at the high-affinity uptake site. The changes in the Km and the Vmax for glutamate uptake were maximal 24 hr after administration of MSO, but the transport system returned to normal by 14 days after injection. In addition, MSO increased high-affinity aspartate uptake into tissue slices, but it was without effect on leucine uptake. Glutamate uptake into striatal synaptosomes and bulk-isolated glial cells or neurons was, in all cases, mediated by a low- and high-affinity carrier. The Km and Vmax values for high-affinity glial-glutamate uptake were increased 24 hr after i.c.v. injection of MSO, while the low-affinity kinetic parameters for glial glutamate uptake were not altered by MSO. Neither high-affinity nor low-affinity glutamate uptake into bulk-isolated neurons or synaptosomes was altered by MSO 24 hr after injection. These results suggest that MSO induced alterations in glutamate transport within striatal slices may be due to changes in glial glutamate transport arising from the disruption of glutamate metabolism.
Rothstein
J D
JD
Tabakoff
B
B
D000818:Animals; D001692:Biological Transport; D003342:Corpus Striatum / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008717:Methionine Sulfoximine / Q000494:pharmacology*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism
D005971:Glutamates; D008717:Methionine Sulfoximine; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase