Effects of 5-aminolevulinic acid on the glutamatergic neurotransmission

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• 作者：Emanuelli ; Tatiana ; Pagel ; Fernanda W. ; Porci&uacute ; ncula ; Lisiane O. ; Souza ; Diogo O.
• 关键词：5-Aminolevulinic acid ; Glutamate binding ; MK-801 binding ; Glutamate uptake ; Astrocytes ; Lipoperoxidation
• 刊名：Neurochemistry International
• 出版年：2003
• 出版时间：January, 2003
• 年：2003
• 卷：42
• 期：2
• 页码：115-121
• 全文大小：131 K

文摘

The haem precursor 5-aminolevulinic acid (ALA) has been proposed to be involved in the neurological dysfunctions presented by patients with acute porphyrias. The effects of ALA on the [³H]glutamate and [³H]MK-801 (dizocilpine) binding to rat cortical membranes and on [³H]glutamate uptake by rat astrocyte cultures were evaluated in the present study in order to elucidate the interaction of ALA with the glutamatergic system and its possible contribution to the in vivo excitatory properties of ALA. ALA (0–1mM) did not affect the binding of 100nM [³H]glutamate, nor the equilibrium binding constants (K_d and B_max) of this neurotransmitter in rat or human cortical membranes. The binding of the NMDA-channel blocker, [³H]MK-801, was not affected by ALA (0–10mM) either. ALA (0–3mM) dose-dependently inhibited glutamate uptake by astrocyte cultures. ALA significantly reduced both the K_m and V_max of glutamate uptake indicating an uncompetitive inhibition. The inhibitory effect was irreversible and apparently related to the selective inhibition of the GLT-1 (EAAT2) subtype of glutamate transporter. The finding that ALA significantly increased astrocyte lipoperoxidation in astrocytes incubated under these conditions suggests that the inhibitory effect of ALA might be related to an oxidative damage of the transporter. We propose that the inhibition of glutamate uptake may underlie ALA-induced convulsions.