Nuclear benzodiazepine binding: Possible interaction with thyroid hormone receptors

The biochemical and pharmacological properties of nuclear ³H]flunitrazepam in brain tissues were studied. Nuclear ³Hflunitrazepam binding is saturable for both central and peripheral binding sites. Inosine and hypoxanthine displace nuclear ³H]flunitrazepam binding with greater potency than the membrane ³H]flunitrazepam binding. Triiodothyronine (T₃) increases the maximum number of binding sites (B_max) of nuclear ³H]flunitrazepam binding in vitro while thyroxine (T₄) does not have any effect. Diazepam reduces the affinity of nuclear¹²⁵I-T₃ binding in vitro, while the B_max is not affected significantly. Mild digestion of chromatin, using micrococcal nuclease, reveals that a major portion of nuclear ³H]flunitrazepam binding sites are located on chromatin. These data suggest a functional role for nuclear benzodiazepine binding and a possible modulatory effect of benzodiazepines on T₃ binding with its nuclear receptors.