title: Inhibition of [3H]quinpirole binding by a monoamine oxidase inhibitor in subcellular fractions of rat striatum.
abstract: [3H]Quinpirole is a dopamine agonist with high affinity for D2-like dopamine receptors. A number of non-dopaminergic compounds, most notably monoamine oxidase inhibitors (MAOIs), inhibit the binding of [3H]quinpirole, but not other D2-like agonists and antagonists, in rat striatal membranes by a mechanism that does not involve the enzymatic activity of MAO. To further characterize this novel interaction, the subcellular distribution of spiperone-displaceable, "D2-like" [3H]quinpirole-labeled sites in rat striatum was assessed and compared with the distribution of MAOI-displaceable [3H]quinpirole binding (MQB). "D2-like" [3H]quinpirole binding exhibited similar nanomolar affinity in the crude synaptosomal (P2), crude microsomal (P3), and ribosomal, post-microsomal (P4) fractions. Total binding activity (fmol bound/fraction) of "D2-like" [3H]quinpirole binding was concentrated in the synaptosomal fraction (P2B). The subcellular distribution of MQB paralleled that of "D2-like" [3H]quinpirole binding. This suggests that "D2-like" [3H]quinpirole binding and MQB occur at a common membrane-bound binding site.
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA. blevant@kumc.edu
authors.forename: B
authors.initials: B
authors.lastname: Levant
authors.forename: G N
authors.initials: GN
authors.lastname: Bancroft
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D018491:Dopamine Agonists / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019257:Quinpirole / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D008996:Monoamine Oxidase Inhibitors; D019257:Quinpirole; D013134:Spiperone