Inhibition of [ 3H]quinpirole binding by a monoamine oxidase inhibitor in subcellular fractions of rat striatum

• Published in: Life sciences (1973) 1998, Vol.63 (18), p.1643-1651
• Main Authors: Levant, Beth, Bancroft, Gregory N.
• Format: Article
• Language: English
• Subjects: [ 3H]quinpirole; Animals; Binding, Competitive - drug effects; Dopamine Agonists - pharmacokinetics; In Vitro Techniques; Male; monoamine oxidase inhibitor; Monoamine Oxidase Inhibitors - pharmacology; Neostriatum - drug effects; Neostriatum - enzymology; Neostriatum - metabolism; Quinpirole - pharmacokinetics; Rats; Rats, Sprague-Dawley; Ribosomes - drug effects; Ribosomes - metabolism; Ro 41-1049; Spiperone - metabolism; striatum; Subcellular Fractions - drug effects; Subcellular Fractions - enzymology; Subcellular Fractions - metabolism; Synaptosomes - drug effects; Synaptosomes - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(98)00433-0

[ 3H]Quinpirole is a dopamine agonist with high affinity for D 2-like dopamine receptors. A number of non-dopaminergic compounds, most notably monoamine oxidase inhibitors (MAOIs), inhibit the binding of [ 3H]quinpirole, but not other D 2-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, “D 2-like” [ 3H]quinpirole-labeled sites in rat striatum was assessed and compared with the distribution of MAOI-displaceable [ 3H]quinpirole binding (MQB). “D 2-like” [ 3H]quinpirole binding exhibited similar nanomolar affinity in the crude synaptosomal (P 2), crude microsomal (P 3), and ribosomal, post-microsomal (P 4) fractions. Total binding activity ( fmol bound fraction ) of “D 2-like” [ 3H]quinpirole binding was concentrated in the synaptosomal fraction (P 2B.) The subcellular distribution of MQB paralleled that of “D 2-like” [ 3H]quinpirole binding. This suggests that “D 2-like” [ 3H]quinpirole binding and MQB occur at a common membrane-bound binding site.