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Free radical modification of high-affinity GABA transport in the central nervous system

Thesis/Dissertation ·
OSTI ID:5006185
Presynaptic nerve terminals of DNS neurons can be characterized as dynamic self-contained subunits of the overall neuron. These neuron subunits together with the adjacent post-synaptic terminals constitute the functional unit of neurotransmission. One major function of the presynaptic nerve terminal in neurotransmission is its role in the release and subsequent reuptake of neurotransmitters. Neurochemical and morphological analysis of this high-affinity uptake process, for the amino acid neurotransmitter gamma-aminobutyric acid (GABA), revealed that free radical modification (lipid peroxidation) of presynaptic nerve terminal membrane structures resulted in a decrease in high-affinity (/sup 14/C)GABA uptake. Depolarized nerve terminals exposed to horseradish peroxidase (HRP)-generated superoxide radicals (.O/sub 2//sup -/) exhibited an alteration of synaptic vesicle membrane structure and a reduction of high-affinity (/sup 14/C)GABA uptake. In the kinetic analysis of high affinity (/sup 14/C)GABA uptake, hypoxanthine/xanthine oxidase (HPX/XOD)-treated synaptosomes exhibited a significant reduction in V/sub max/ but no significant alteration of K/sub m/. This HPX/XOD treatment also resulted in significant structural alterations of both the synaptic vesicle membrane and the synaptosomal plasma membrane. Structural and functional correlates appear to exist between synaptic vesicle and plasma membrane systems and high-affinity (/sup 14/C)GABA uptake. Together, the selectivity of the .O/sub 2//sup -/ toxicity and that of the high-K/sup +//Na/sup +/-free effect support the idea of two separate and different amino acid uptake systems in CNS tissue.
Research Organization:
New York Univ., NY (USA)
OSTI ID:
5006185
Country of Publication:
United States
Language:
English

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Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMAL CELLS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
DRUGS
KINETICS
LABELLED COMPOUNDS
NERVE CELLS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
RADICALS
REACTION KINETICS
SOMATIC CELLS
SUPEROXIDE RADICALS
UPTAKE