title: Astroglia-released factor with negative allosteric modulatory properties at the GABA A receptor.
abstract: We have previously shown, using whole-cell patch-clamp techniques, that astrocytes release a negative allosteric modulator of the gamma-aminobutyric acid type A receptor (GABAA receptor) with beta-carboline-like properties, thus, likely to act at the benzodiazepine site. Here, using patch-clamp and binding techniques, we confirm that the low-molecular-weight fraction of astroglia-conditioned medium (ACM lmf) contains a factor(s) that negatively modulates GABAA-receptor function. This factor, like beta-carbolines, enhances the specific binding of [35S]t-butyl bicyclophosphorothionate (TBPS) to adult rat cortical membranes in the presence of GABA. However, it fails to interact with various ligands of the benzodiazepine (BZD) site of the GABAA receptor ([3H]flunitrazepam, [3H]Ro 15-1788 and [3H]Ro 15-4513). The question of the actual binding site of the astroglia-derived factor on the GABAA receptor, thus, remains open and can be addressed only after the purification of the active molecule(s) of ACM Imf has been completed, and a labeled form of the endogenous ligand becomes available. Taken together, however, the data suggest that type 1 astrocytes are able to modulate the effects of the main inhibitory neurotransmission in the central nervous system.
authors.affiliation: Laboratory of Human Physiology and Pathophysiology, University of Liège, Belgium.
authors.forename: J M
authors.initials: JM
authors.lastname: Rigo
authors.forename: S
authors.initials: S
authors.lastname: Belachew
authors.forename: P
authors.initials: P
authors.lastname: Coucke
authors.forename: P
authors.initials: P
authors.lastname: Leprince
authors.forename: B
authors.initials: B
authors.lastname: Malgrange
authors.forename: B
authors.initials: B
authors.lastname: Rogister
authors.forename: G
authors.initials: G
authors.lastname: Moonen
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005445:Flunitrazepam / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D010455:Peptides; D011963:Receptors, GABA-A; D005445:Flunitrazepam