"Peripheral type" benzodiazepine binding sites in rat adrenals: binding studies with [3H]PK 11195 and...

PK 11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinec arboxamide] is a compound chemically unrelated to benzodiazepines with a high affinity for the "peripheral type" binding sites for benzodiazepines (Le Fur et al., 1983a). [3H]PK 11195 binds to the adrenal membranes with a high affinity (KD congruent to 3 nM) in a specific, reversible and GABA-independent manner. Binding is also characterized by very high Bmax (34 pmol/mg protein). These binding sites are the "peripheral type" benzodiazepine binding sites as demonstrated by the potency order of displacement of the [3H]PK 11195 bound: PK 11195 greater than R05-4864 greater than diazepam greater than dipyridamole greater than clonazepam. The biochemical characteristic of the binding to rat adrenal sections has also been studied. In these conditions the affinity for [3H]PK 11195 is ten times smaller, but the potency order of displacing agents was the same, demonstrating the identity of the section binding sites. Using tritium sensitive film these sites have been visualized in adrenal sections. [3H]PK 11195 binding sites are localized in the adrenal cortex with some spare labelling in the medulla.