title: Pharmacology of quinpirole-stimulated [35S]GTPgammaS binding: discrepancy with receptor binding profile.
abstract: Functional consequences of receptor stimulation by quinpirole, a dopamine D(2)-like receptor agonist, were assessed using agonist-stimulated [35S]GTPgammaS binding in rat striatal membranes. Dopamine receptor antagonists inhibited quinpirole-stimulated [35SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine), consistent with a dopamine D(2)-like profile. In contrast, the monoamine oxidase inhibitors Ro 41-1049 (N-(2-aminoethyl)-5-(3-fluorophenyl)-4-thiazolecarboxemide), and (+)- and (-)-deprenyl, which inhibit [3H]quinpirole binding, had no effect on agonist-independent or quinpirole-stimulated [35S]GTPgammaS binding. Clorgyline inhibited [35S]GTPgammaS binding by a non-dopamine D(2) receptor-mediated mechanism. These findings demonstrate a notable discrepancy between the pharmacological profile of [3H]quinpirole binding and quinpirole-stimulated [35S]GTPgammaS binding.
authors.affiliation: Departments of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160-7147, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Gilliland
authors.forename: R H
authors.initials: RH
authors.lastname: Alper
authors.forename: B
authors.initials: B
authors.lastname: Levant
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D003010:Clorgyline / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D013462:Sulfur Radioisotopes; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D008996:Monoamine Oxidase Inhibitors; D017448:Receptors, Dopamine D2; D013462:Sulfur Radioisotopes; D013844:Thiazoles; D019257:Quinpirole; D012642:Selegiline; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C063456:Ro 41-1049; D013134:Spiperone; D003024:Clozapine; D006220:Haloperidol; D003010:Clorgyline