title: [3H]quinpirole binding to putative D2 and D3 dopamine receptors in rat brain and pituitary gland: a quantitative autoradiographic study.
abstract: The putative D2 dopamine receptor agonist quinpirole (LY 171,555) has been extensively used in a variety of in vivo and in vitro studies of D2 receptor-mediated effects and may have even higher affinity for the recently described D3 dopamine receptor. In the present study, conditions for autoradiographic visualization of [3H]quinpirole-labeled D2-like dopamine receptors were optimized and binding to slide-mounted sections was characterized with respect to pharmacology, guanine nucleotide sensitivity and regional distribution. The pharmacological profile of [3H]quinpirole binding in slide-mounted brain sections was: (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene > or = quinpirole > dopamine for putative dopamine agonists; spiperone > (+)-butaclamol > (-)-sulpiride > SCH 23390 >> cinanserin > (-)-butaclamol for antagonists. [3H]Quinpirole binding was decreased in the presence of guanine nucleotides in most brain regions except in the islands of Calleja and the molecular layer of cerebellar lobules 9 and 10. The regional distribution of [3H]quinpirole binding sites roughly paralleled the distribution of [3H]-(-)-sulpiride binding sites, with greatest densities present in the olfactory bulb glomerular layer, islands of Calleja, pituitary intermediate lobe, caudate/putamen, olfactory tubercles and nucleus accumbens. However, significantly greater densities of [3H]quinpirole binding than [3H]-(-)-sulpiride binding were observed in the molecular layer of cerebellar lobules 9 and 10, the islands of Calleja and olfactory bulb glomerular layer in concordance with the recently reported distribution of D3 receptor mRNA in these brain regions. Higher concentrations of [3H]quinpirole binding were also observed in the dorsomedial caudate and pituitary intermediate lobe. These data indicate the utility of [3H]quinpirole to label D3 as well as D2 dopamine receptors.
authors.affiliation: Central Nervous System Diseases Research, DuPont Merck Pharmaceutical Company, Wilmington, Delaware.
authors.forename: B
authors.initials: B
authors.lastname: Levant
authors.forename: D E
authors.initials: DE
authors.lastname: Grigoriadis
authors.forename: E B
authors.initials: EB
authors.lastname: DeSouza
mesh_terms: D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001923:Brain Chemistry; D004873:Ergolines / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D010902:Pituitary Gland / Q000737:chemistry*; D019257:Quinpirole; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000032:analysis*; D017448:Receptors, Dopamine D2 / Q000032:analysis*; D050637:Receptors, Dopamine D3; D013469:Sulpiride / Q000378:metabolism
chemical_list: C493595:Drd3 protein, rat; D004873:Ergolines; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019257:Quinpirole; D006165:Guanylyl Imidodiphosphate; D013469:Sulpiride