Nuclear benzodiazepine binding: possible interaction with thyroid hormone receptors.
The biochemical and pharmacological properties of nuclear [3H]flunitrazepam in brain tissues were studied. Nuclear [3H]flunitrazepam 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 (Bmax) of nuclear [3H]flunitrazepam binding in vitro while thyroxine (T4) does not have any effect. Diazepam reduces the affinity of nuclear 125I-T3 binding in vitro, while the Bmax 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.
Dalezios
Y
Y
Department of Biology, University of Patras, Greece.
Matsokis
N
N
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology
D007042:Hypoxanthines; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D001569:Benzodiazepines; D019271:Hypoxanthine; D007288:Inosine; D005445:Flunitrazepam; D004247:DNA; D013974:Thyroxine