Arachidonic acid inhibits 3H-glutamate uptake with different potencies in rodent central nervous system regions expressing different transporter subtypes.
High-affinity glutamate reuptake in neurons and glial cells, a mechanism involved in the maintenance of physiological excitatory amino acid neurotransmission, can be inhibited by arachidonic acid (AA). We studied the effect of different doses (from 10 to 500 microM) of AA on L-[3H]glutamate uptake in synaptosomes from rat cortex, rat cerebellum and mouse spinal cord. We found that AA inhibition was dose-dependent, but the IC50 in the cortex differed significantly from those in the cerebellum and spinal cord (170+/-7.9 microM vs 42.5+/-5.4 microM and 34.7+/-2.2 microM respectively). We therefore suggest that arachidonic acid modulates uptake differently in relation to the regional expression of the glutamate transporter subtypes.
Manzoni
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C
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Mennini
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T
D018528:ATP-Binding Cassette Transporters / Q000145:classification / Q000187:drug effects* / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D014179:Neurotransmitter Uptake Inhibitors; D016718:Arachidonic Acid; D018698:Glutamic Acid