Cellular distribution and regulation by cAMP of the GABA transporter (GAT-1) mRNA.
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.
Gomeza
J
J
Departamento de Biología Molecular, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Giménez
C
C
Zafra
F
F
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D050485:GABA Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D027361:Organic Anion Transporters; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009838:Oligodeoxyribonucleotides; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C493415:Slc6a1 protein, rat; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D005680:gamma-Aminobutyric Acid; D003994:Bucladesine; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate