Pharmacological characteristics of diazepam receptors in neurons and astrocytes in primary cultures

• Published in: Journal of neuroscience research Vol. 18; no. 2; p. 366
• Main Authors: Bender, A S, Hertz, L
• Format: Journal Article
• Language: English
• Published: United States 1987
• Subjects: Animals; Anti-Anxiety Agents - pharmacology; Astrocytes - metabolism; Benzodiazepines - antagonists & inhibitors; Cells, Cultured; Diazepam - metabolism; Mice; Neurons - metabolism; Receptors, GABA-A - drug effects; Receptors, GABA-A - metabolism
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490180215

Benzodiazepine binding sites in mouse astrocytes and neurons in primary cultures were labeled with [3H]diazepam (1.8 nM), and their inhibition by 14 different benzodiazepines and 3 benzodiazepine antagonists was studied. RO 5-4864, RO 7-3351, and, especially, the antagonist PK 11195 were much more potent in astrocytes than in neurons, whereas the opposite was true for the agonists alprazolam, clonazepam, flurazepam, RO 11-3128, and chlordiazepoxide, and, especially, the antagonists CGS-8216 and RO 15-1788. Flunitrazepam, diazepam, midazolam, RO 11-6893, and RO 5-2181 were about equipotent in the two cell types. The neuronal, but not the astrocytic, binding site showed stereospecificity. In astrocytes most of the drugs had pseudo-Hill coefficients close to one, whereas the pseudo-Hill coefficients in neurons, except for RO 5-4864 and PK 11195, were distinctly lower than one. Thus, the benzodiazepine binding sites had profoundly different pharmacological characteristics in neurons and in astrocytes.