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Uptake, Release, and Metabolism of Citrate in Neurons and Astrocytes in Primary Cultures
Author(s) -
Westergaard Niels,
Sonnewald Ursula,
Unsgård Germund,
Peng Liang,
Hertz Leif,
Schousboe Arne
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.62051727.x
Subject(s) - citrate synthase , cerebellum , biochemistry , glutamate receptor , granule (geology) , metabolism , biology , extracellular , neurotransmitter , neuron , enzyme , chemistry , endocrinology , neuroscience , receptor , paleontology
Abstract: Synthesis, uptake, release, and oxidative metabolism of citrate were investigated in neurons and astrocytes cultured from cerebral cortex or cerebellum. In addition, the possible role of citrate as a donor of the carbon skeleton for biosynthesis of neurotransmitter glutamate was studied. All cell types expressed the enzyme citrate synthase at a high activity, the cerebellar granule neurons containing the enzyme at a higher activity than that found in the astrocytes from the two brain regions or the cortical neurons. Saturable citrate uptake could not be detected in any of the cell types, but the astrocytes, and, in particular, those of cerebellar origin, had a very active de novo synthesis and release of citrate (∼70 nmol × h −1 × mg of protein −1 ). The rate of release of citrate from neurons was <5% of this value. Using [ 14 C]citrate it could be shown that citrate was oxidatively metabolized to 14 CO 2 at a modest rate (∼1 nmol × n −1 × mg −1 of protein) with slightly higher rates in astrocytes compared with neurons. Experiments designed to investigate the ability of exogenously supplied citrate to serve as a precursor for synthesis of transmitter glutamate in cerebellar granule neurons failed to demonstrate this. Rather than citrate serving this purpose it may be suggested that astrocytically released citrate may regulate the extracellular concentration of Ca 2+ and Mg 2+ by chelation, thereby modulating neuronal excitability.