Benzodiazepine binding sites in human pineal gland.

The high affinity binding of [3H]flunitrazepam (FNZP) to crude membrane preparations was examined in human pineal glands. Scatchard analysis of the data at equilibrium revealed a single population of binding sites with dissociation constant = 2.36-2.53 nM and binding site concentration = 59-108 fmol/mg protein. When various benzodiazepine (BZP) analogues were tested for their ability to inhibit [3H]FNZP binding the following Ki (nM) were found: clonazepam (0.13), RO 15-1788 (0.60), FNZP (2.14), diazepam (13.5), Ro 5-4864 (greater than 10 000). In both human pineal gland and cerebral cortex 10-100 microM gamma-aminobutyric acid (GABA) increased BZP binding by about 30%, an effect inhibited by the GABA receptor blocker bicuculline. The stimulatory effect of GABA on [3H]FNZP binding in rat cerebral cortex (about 60%) decreased as a function of time elapsed postmortem at room temperature to reach values similar to those observed in human brains. These results suggest the existence of central type BZP receptors in the human pineal glands.