title: Differential effect of detergents on [3H]Ro 5-4864 and [3H]PK 11195 binding to peripheral-type benzodiazepine-binding sites.
abstract: The present study demonstrates a differential effect of various detergent treatments on [3H]Ro 5-4864 and [3H]PK 11195 binding to peripheral benzodiazepine binding sites (PBS). Triton X-100 (0.0125%) caused a decrease of about 70% in [3H]Ro 5-4864 binding to membranes from various peripheral tissues of rat, but had only a negligible effect on [3H]PK 11195 binding. A similar effect of Triton X-100 was observed on guinea pig and rabbit kidney membranes. The decrease in [3H]Ro 5-4864 binding after treatment with Triton X-100 was apparently due to a decrease in the density of PBS, since the affinity remained unaltered. The detergents 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS), Tween 20, deoxycholic acid, or digitonin (0.0125%) caused only a minor change in [3H]Ro 5-4864 and [3H]PK 11195 binding to rat kidney membranes; but when concentrations were substantially increased (0.1%), all detergents caused a decrease of at least 50% in [3H]Ro 5-4864 binding, while [3H]PK 11195 binding to rat kidney membranes remained unaffected by the first three detergents, with only a minor decrease (15%) after treatment with digitonin. These results may further support the assumption that Ro 5-4864 and PK 11195 are agonist and antagonist, respectively, of PBS and interact with two different conformations or domains in the peripheral-type benzodiazepine binding site molecule.
authors.affiliation: Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Awad
authors.forename: M
authors.initials: M
authors.lastname: Gavish
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism*; D003292:Convulsants; D003902:Detergents / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013501:Surface-Active Agents / Q000494:pharmacology*
chemical_list: D001570:Benzodiazepinones; D003292:Convulsants; D003902:Detergents; D007546:Isoquinolines; D011963:Receptors, GABA-A; D013501:Surface-Active Agents; C028513:4'-chlorodiazepam; D011092:Polyethylene Glycols; D017830:Octoxynol; C037850:PK 11195