Arachidonic acid inhibits H-3-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 mu M) of AA on L-[H-3]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 mu M vs 42.5+/-5.4 mu M and 34.7+/-2.2 mu M respectively). We therefore suggest that arachidonic acid modulates uptake differently in relation to the regional expression of the glutamate transporter subtypes. (C) 1997 The Italian Pharmacological Society.