Chemical modification showing the difference between central- and peripheral-type benzodiazepine receptors

The binding of [3H]flunitrazepam ([3HlFNZP) to the peripheral-type benzodiazepine binding sites in rat kidney was characterized. The binding was reversible. relatively high-affinity (KD = 19+6 nmol/L), saturable. and inhibited by some benzodiaze-pines (BZS) such as R0 5-4864, FNZP etc. Therefore, these sites could classified as peripheral benzodiazepine receptors (BZ-R). The differences of peripheral BZ-R and central BZ-R were as follows: Clonazepam was the most, and R0 5-4864 the least, potent in displacing [3H]FNZP from the central BZ-R. while the relative affinities of clonazepam and R0 5-4864 for the peripheral BZ-R were just the reverse of that in central BZ-R of rat brain homogenates. Our results indicate that BZS such as estazolam, R0 15-1788, delorazepam and flurazepam can effectively displace [3H]FNZP from central BZ-R but not peripheral BZ-R. The peripheral BZ-R can not be photolabeled with [3H]FNZP. The chemical modification suggests that the binding areas of peripheral BZ-R and central BZ-R may be different. The cysteine residue may be a necessary functional group in peripheral BZ-R, but not in central BZ-R.