Effect of benzodiazepines and pentobarbital on the GABA-induced depolarization in cultured astrocytes.
We have previously shown that cultured astrocytes from neonatal rat cerebral cortex are depolarized by GABA. The underlying ionic mechanism, activation of a Cl- conductance and responses to an agonist and antagonists were found to be similar to those of the neuronal GABAA receptor (Kettenmann et al.: Brain Research 404:1-9, 1987; Kettenmann and Schachner: Journal of Neuroscience 5:3295-3301, 1985). To characterize further the pharmacological properties of the GABA receptor we have tested the influence of pentobarbital and benzodiazepines on the GABA response. Pentobarbital potentiated and prolonged the GABA-induced depolarization and enhanced the velocity of the depolarization. Agonists of the neuronal benzodiazepine receptor, flunitrazepam, diazepam, and midazolam, increased the GABA-induced depolarization. As in neurons, an antagonist of the benzodiazepine receptor, Ro 15-1788, blocked the flunitrazepam-induced enhancement of the GABA response. In contrast to their effects on neurons, the inverse agonists Ro 22-7497 and DMCM increased the GABA-induced depolarization. The ligand of the putative peripheral benzodiazepine binding site, Ro 5-4864, did not show consistent effects on the GABA response. These studies confirm that cultured astrocytes express GABAA receptors. This receptor is similar to the neuronal GABAA receptor with regard to Cl- conductance and its pharmacological responses to muscimol, bicuculline, picrotoxin, pentobarbital, and benzodiazepine agonists and an antagonist, but it is different in its responses to inverse agonists of the benzodiazepine site. The physiological role of the glial GABAA receptor is at present unknown.
Backus
K H
KH
Department of Neurobiology, University of Heidelberg, Federal Republic of Germany.
Kettenmann
H
H
Schachner
M
M
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005445:Flunitrazepam / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001570:Benzodiazepinones; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C028513:4'-chlorodiazepam; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D010424:Pentobarbital