title: [3H]Pramipexole: a selective radioligand for the high affinity dopamine D2 receptor in bovine striatal membranes.
abstract: The characterization of [3H]pramipexole binding to bovine striatal membranes is reported in full experimental detail. According to kinetic experiments, saturation and competition studies a single binding site can be selectively labeled which turned out to be the high affinity D2 receptor. Addition of GPP(NH)P resulted in almost complete loss of specific binding. The bovine D2 subtype shows high sequence identity with the human D2 receptor indicating that the heterologous competition assays are of interest for the evaluation of neurotropic drug candidates. Using the representative D2 agonists (+)-7-OH-DPAT, (-)-3-PPP and (S)-7-dipropylaminotetrahydroindolizine the same rank order of affinities was determined as described for rat striata labeled with [3H]pramipexole, however, the Ki values turned out to be significantly higher. Furthermore, the system facilitates structure activity relationship studied on D2 affinity modulating peptides. Using L-prolyl-L-leucyl-glycinamide as an example a significant increase of specific radioligand binding could be measured.
authors.affiliation: Institut für Pharmazie und Lebensmittelchemie der Universität Erlangen-Nürnberg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Ohnmacht
authors.forename: C
authors.initials: C
authors.lastname: Tränkle
authors.forename: K
authors.initials: K
authors.lastname: Mohr
authors.forename: P
authors.initials: P
authors.lastname: Gmeiner
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D052160:Benzothiazoles; D001667:Binding, Competitive; D002417:Cattle; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D000077487:Pramipexole; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D013134:Spiperone / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D001552:Benzazepines; D052160:Benzothiazoles; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D008024:Ligands; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013844:Thiazoles; D013134:Spiperone; D000077487:Pramipexole