Properties of [3H] ß-carboline-3-carboxylate ethyl ester binding to the benzodiazepine receptor

β-Carbolines are inhibitors of ³H] diazepam binding with the most potent inhibitor being β-carboline-3-carboxylate ethyl ester (β-CCE). In this report the binding of ³H] β-CCE to extensively washed rat forebrain membranes is characterized. ³H] ß-CCE binds with high affinity (K_D = 1.4 nM) to an apparently homogenous population of benzodiazepine receptor. The rank order of potency for inhibition of ³H] ß-CCE binding by different benzodiazepines is clonazepam > diazepam > chlordiazepoxide, which is similar to that observed for inhibition of ³H] diazepam binding. In marked contrast to ³H] diazepam, the binding of ³H] ß-CCE is not modulated by GABA since concentrations of GABA as high as 10^?3 M had no effect. ³H] ß-CCE is also less potent than ³H] diazepam in its interaction with the peripheral type kidney benzodiazepine receptor indicating that this ligand has a higher degree of specificity for the central brain type benzodiazepine receptor.