Astroglial Cells Express Large Amounts of GABAA Receptor Proteins in Mature Brain |
| |
Authors: | † Michel Bureau †Jacques Laschet Mercédès Bureau-Heeren Benoît Hennuy Arlette Minet Pierre Wins Thierry Grisar |
| |
Institution: | Laboratory of Neurochemistry, University of Liège, Liège, Belgium;and; INSERM CJF 90-12, University of Rennes, Rennes, France |
| |
Abstract: | Abstract: GABAA receptors were characterized in cellular fractions isolated from adult bovine brain. The fraction enriched in cortical astrocytes is very rich in high-affinity binding sites for 3H]flunitrazepam and other "central-type" benzodiazepine ligands. The amount of specific 3H]flunitrazepam binding was more than five times higher in the glial fraction than in synaptosomal and perikaryal fractions. 3H]Flunitrazepam was displaced by low concentrations of clonazepam and other specific ligands for central GABAA receptors. Specific binding sites for GABA, flunitrazepam, barbiturates, and picrotoxin-like convulsants were characterized. Allosteric interactions between the different sites were typical of central-type GABAA receptors. The presence of α-subunit(s), as revealed by 3H]flunitrazepam photoaffinity labeling, was demonstrated in all brain fractions at molecular mass 51–53 kDa. Photoaffinity labeling was highest in the glial fraction. However, in primary cultured astrocytes from neonate rat cortex, no photoaffinity labeling was detected. Information obtained from astrocytes in culture should thus be taken with caution when extrapolated to differentiated astroglial cells. Our results actually show that, in mature brain, most of the fully pharmacologically active GABAA receptors are extrasynaptic and expressed in astroglia. |
| |
Keywords: | GABAA receptor Astrocyte Benzodiazepine Allosteric modulation Photoaffinity labeling Tissue fractionation |
|
|