Abstract
The high-affinity GABA transporter in neurons and glial cells is the primary means of inactivating synaptic GABA. In the present study, a rat GABA transporter (GAT-1)-specific probe was used to quantitate GAT-1 mRNA in cultured neurons and glial cells from rat brain. GAT-1 mRNA is expressed in neurons but not in pure cultures of astrocytes. Incubation of neurons with forskolin led to concentration- and time-dependent decreases in GAT-1 mRNA. This effect could be also achieved by chronic exposure of neurons to 8-Br-cAMP and dib-cAMP but not with 1,9-dideoxyforskolin. This effect on the levels of GAT-1 mRNA correlates with a decrease in the Na(+)-dependent GABA transport activity in neurons. Treatment with agents that increase cellular levels of cAMP did not affect GABA transport or GAT-1 mRNA expression in glial cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Animals
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Animals, Newborn
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / metabolism*
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Base Sequence
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Bucladesine / pharmacology
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Carrier Proteins / biosynthesis
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Carrier Proteins / metabolism*
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / metabolism*
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Cloning, Molecular
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Colforsin / pharmacology*
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Cyclic AMP / metabolism*
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GABA Plasma Membrane Transport Proteins
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Gene Expression Regulation*
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Glial Fibrillary Acidic Protein / analysis
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Immunohistochemistry
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Kinetics
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Membrane Proteins / biosynthesis
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Membrane Proteins / metabolism*
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Membrane Transport Proteins*
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Molecular Sequence Data
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Neuroglia / cytology
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Neuroglia / drug effects
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Neuroglia / metabolism*
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Oligodeoxyribonucleotides
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Organic Anion Transporters*
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RNA, Messenger / analysis
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RNA, Messenger / metabolism*
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Rats
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Rats, Wistar
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Tetradecanoylphorbol Acetate / pharmacology
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Time Factors
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gamma-Aminobutyric Acid / metabolism*
Substances
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Carrier Proteins
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GABA Plasma Membrane Transport Proteins
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Glial Fibrillary Acidic Protein
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Membrane Proteins
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Membrane Transport Proteins
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Oligodeoxyribonucleotides
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Organic Anion Transporters
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RNA, Messenger
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Slc6a1 protein, rat
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Colforsin
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8-Bromo Cyclic Adenosine Monophosphate
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gamma-Aminobutyric Acid
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Bucladesine
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Cyclic AMP
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Tetradecanoylphorbol Acetate