Levant B, Grigoriadis D E, DeSouza E B
Central Nervous System Diseases Research, DuPont Merck Pharmaceutical Company, Wilmington, Delaware.
J Pharmacol Exp Ther. 1993 Feb;264(2):991-1001.
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.
假定的D2多巴胺受体激动剂喹吡罗（LY 171,555）已被广泛用于各种D2受体介导效应的体内和体外研究，并且对最近描述的D3多巴胺受体可能具有更高的亲和力。在本研究中，优化了[3H]喹吡罗标记的D2样多巴胺受体放射自显影可视化的条件，并从药理学、鸟嘌呤核苷酸敏感性和区域分布方面对与载玻片上的切片的结合进行了表征。载玻片上脑切片中[3H]喹吡罗结合的药理学特征为：对于假定的多巴胺激动剂，（+/-）-2-氨基-6,7-二羟基-1,2,3,4-四氢萘≥喹吡罗＞多巴胺；对于拮抗剂，螺哌隆＞（+）-布他拉莫＞（-）-舒必利＞SCH 23390＞西那色林＞（-）-布他拉莫。除了Calleja岛以及小脑小叶9和10的分子层外，在大多数脑区中，鸟嘌呤核苷酸的存在会降低[3H]喹吡罗的结合。[3H]喹吡罗结合位点的区域分布大致与[3H]-（-）-舒必利结合位点的分布平行，在嗅球肾小球层、Calleja岛、垂体中间叶、尾状核/壳核、嗅结节和伏隔核中密度最大。然而，在小脑小叶9和10的分子层、Calleja岛和嗅球肾小球层中，观察到[3H]喹吡罗结合的密度明显高于[3H]-（-）-舒必利结合，这与最近报道的这些脑区中D3受体mRNA的分布一致。在背内侧尾状核和垂体中间叶也观察到较高浓度的[3H]喹吡罗结合。这些数据表明[3H]喹吡罗可用于标记D3以及D2多巴胺受体。
