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

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.