Computer-assisted determination of benzodiazepine receptor heterogeneity

The presence of benzodiazepine receptor heterogeneity was investigated on whole rat brain membranes, at 0 degree C, using computerized, weighted nonlinear least-squares regression analysis. Data from [3H]flunitrazepam and [3H] beta-carboline ethyl ester self and cross-competition studies were analyzed simultaneously with data from the inhibition of both labeled ligands by various known and novel benzodiazepine receptor ligands. The binding model which best fits the data indicated the presence of at least two independent binding sites. The benzodiazepines flunitrazepam and 2'-Cl-diazepam showed a small difference in affinity at the two sites. The beta-carbolines and Cl 218,872 showed a larger difference in affinity, and had higher affinities at the lower affinity site for the benzodiazepines. Analogous experiments could be useful in the determination of the effect of GABA on benzodiazepine receptor affinities.