Benzodiazepines that bind at peripheral sites inhibit cell proliferation.
[3H]Ro5-4864 binds to mouse thymoma cells in a specific, saturable, and reversible manner. Scatchard analysis shows a single class of binding sites with a Kd of 4.4 nM and a Bmax of 477 fmol per 10(6) cells. This benzodiazepine binding site is of the peripheral type, based on the relative potencies of Ro5-4864 and clonazepam in competing for [3H]diazepam binding. Fifteen benzodiazepines that bind to this site with affinities ranging from 6 nM to 1 microM also reversibly inhibit the proliferation of thymoma cells in culture at the micromolar dose range. There is a strong positive correlation (r = 0.85) between the binding constants of these compounds for the peripheral-type sites and their ED50 in inhibiting the uptake of [3H]thymidine into the cells. These sites may be involved in the regulation of thymoma cell proliferation.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines / Q000378:metabolism*; D001570:Benzodiazepinones / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects*; D051379:Mice; D008806:Mice, Inbred AKR; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013945:Thymoma / Q000503:physiopathology; D013953:Thymus Neoplasms / Q000503:physiopathology
D000927:Anticonvulsants; D001570:Benzodiazepinones; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C028513:4'-chlorodiazepam