title: Dopamine D1 receptors labelled with [3H]SCH23390 in rabbit cerebral cortex and neostriatum. Equilibrium binding, kinetics and selectivity.
abstract: The binding characteristics of the novel benzazepine compound SCH23390 were studied using membrane preparations from rabbit cerebral cortex (CTX) and neostriatum (CPU; caudate putamen). The association kinetics of [3H]SCH23390 to membranes from CTX and CPU were rapid, while the dissociation kinetics were extremely slow and only around 40-60% of the binding was displaced two hours after the addition of either S(+)-butaclamol or 30 volumes of buffer. The saturation curves revealed that [3H]SCH23390 bound with high affinity in both tissues, with densities of 133 fmol/mg protein for CTX (Kd 25 degrees C = 0.31 nM) and 664 fmol/mg protein for CPU (Kd = 0.13 nM). the specificity of binding to the cortical D1 receptor was verified in competition experiments with a variety of dopaminergic agents. The rank order of potency of these compounds was consistent with the pharmacology of the dopaminergic D1 site. All competition curves were better fitted to a one-site model with Hill coefficients around one, indicating that [3H]SCH23390 was binding to a single cortical site. The stereoselectivity of the cortical [3H]SCH23390 binding site could be demonstrated by the use of enantiomer pairs of dopaminergic drugs. This study provides compelling evidence that [3H]SCH23390 binds to dopamine D1 receptors in the neostriatum and cerebral cortex of the rabbit.
authors.affiliation: Département de Physiologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
authors.forename: T A
authors.initials: TA
authors.lastname: Reader
authors.forename: L
authors.initials: L
authors.lastname: Grondin
authors.forename: B
authors.initials: B
authors.lastname: Montreuil
authors.forename: K M
authors.initials: KM
authors.lastname: Dewar
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D011817:Rabbits; D011954:Receptors, Dopamine / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D001552:Benzazepines; D015259:Dopamine Agents; D011954:Receptors, Dopamine