BINDING OF A NOVEL DOPAMINERGIC AGONIST RADIOLIGAND [H-3] FENOLDOPAM1 (SKF 82526) TO D-1 RECEPTORS IN RAT STRIATUM
BINDING OF A NOVEL DOPAMINERGIC AGONIST RADIOLIGAND [H-3] FENOLDOPAM1 (SKF 82526) TO D-1 RECEPTORS IN RAT STRIATUM
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DOI：
10.1016/0024-3205(85)90049-9
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发表时间：
1985-01-01
期刊：
影响因子：
6.1
通讯作者：
WEINSTOCK, J
中科院分区：
文献类型：
--
作者：
FLAIM, KE;GESSNER, GW;WEINSTOCK, J
非诺多泮（SKF 82526）是一种表现出D-1受体亚型选择性的多巴胺激动剂，被评价为该受体亚型的放射性配体。在大鼠纹状体膜制备物的饱和研究中，[3 H]-非诺多泮似乎标记单个结合位点，Kd为2.3 ±。0.1 nM和Bmax [最大结合能力]为590 ± 0.001 nM。40 fmol/mg蛋白质。在竞争结合实验中，结合被证明是立体选择性的;多巴胺能和非多巴胺能化合物的亲和力的等级排序与这些化合物在刺激或抑制多巴胺敏感性腺苷酸环化酶（D-1）和结合到用拮抗剂[3 H]-顺式-氟哌噻吨标记的D-1位点中的效力密切相关。最有效的竞争者是最近发现的D-1选择性拮抗剂SCH 23390 [S-（+）-8-氯-2，3，4，5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7-醇]和SKF R-83566 [7-溴-8-羟基-3-甲基-1-苯基-2，3，4，5-四氢-1H-3-苯并氮杂卓]。[3 H]-非诺多泮也用于评估激动剂D-1受体相互作用。显然，[3 H]-非诺多泮是D-1受体的有用的和选择性激动剂放射性配体。
Fenoldopam (SKF 82526), a dopamine agonist which exhibits D-1 receptor subtype selectivity, was evaluated as a radioligand for this receptor subtype. In saturation studies in rat striatal membrane preparations, [3H]-fenoldopam appeared to label a single binding site with Kd of 2.3 .+-. 0.1 nM and a Bmax [maximal binding capacity] of 590 .+-. 40 fmoles/mg protein. In competition binding experiments, binding was shown to be stereoselective; rank ordering of affinities of dopaminergic and non-dopaminergic compounds closely correlated with potencies of these compounds in stimulating or inhibiting dopamine-sensitive adenylate cyclase (D-1) and in binding to D-1 sites labeled with the antagonist [3H]-cis-flupenthixol. The most potent competitors were the recently identified D-1 selective antagonists, SCH 23390 [S-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol] and SKF R-83566 [7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazephrine]. [3H]-Fenoldopam was also used to assess agonist D-1 receptor interactions. Apparently, [3H]-fenoldopam is a useful and selective agonist radioligand for the D-1 receptor.