Altar C A, Marien M R
J Neurosci. 1987 Jan;7(1):213-22. doi: 10.1523/JNEUROSCI.07-01-00213.1987.
Iodinated SCH 23390, 125I-SCH 23982 (DuPont-NEN), was examined using quantitative autoradiography for its potency, selectivity, and anatomical and neuronal localization of binding to the dopamine D1 receptor in rat brain sections. 125I-SCH 23982 bound to D1 sites in the basal ganglia with very high affinity (Kd values of 55-125 pM), specificity (70-85% of binding was displaced by 5 microM cis-flupenthixol), and in a saturable manner (Bmax values of 65-176 fmol/mg protein). Specific 125I-SCH 23982 binding was displaced by the selective D1 antagonists SCH 23390 (IC50 = 90 pM) and cis-flupenthixol (IC50 = 200 pM) and the D1 agonist SKF 38393 (IC50 = 110 nM) but not by D2-selective ligands (I-sulpiride, LY 171555) or the S2 antagonist cinanserin. Compared with 3H-SCH 23390, the 5- to 10-fold greater affinity for the D1 site and 50-fold greater specific radioactivity of 125I-SCH 23982 makes it an excellent radioligand for labeling the D1 receptor. The concentrations of D1 sites were greatest in the medial substantia nigra and exceeded by over 50% the concentration of D1 sites in the lateral substantia nigra, caudoputamen, nucleus accumbens, olfactory tubercle, and entopeduncular nucleus. Lower concentrations of D1 sites were present in the internal capsule, dorsomedial frontal cortex, claustrum, and layer 6 of the neocortex. D1 sites were absent in the ventral tegmental area. Intrastriatal injections of the axon-sparing neurotoxin, quinolinic acid, depleted by 87% and by 46-58% the concentrations of displaceable D1 sites in the ipsilateral caudoputamen and medial and central pars reticulata of the substantia nigra, respectively. No D1 sites were lost in the lateral substantia nigra. Destruction of up to 94% of the mesostriatal dopaminergic projection with 6-hydroxydopamine did not reduce D1 binding nor, with one exception, increase striatal or nigral D1 receptor concentrations. 125I-SCH 23982 selectively labels D1 binding sites on striatonigral neurons with picomolar affinity, and these neurons contain the majority of D1 sites in rat brain.
使用定量放射自显影技术对碘化的SCH 23390（125I-SCH 23982，杜邦-新英格兰核公司）在大鼠脑切片中与多巴胺D1受体结合的效力、选择性、解剖学定位和神经元定位进行了研究。125I-SCH 23982以非常高的亲和力（解离常数Kd值为55 - 125皮摩尔）、特异性（5微摩尔顺式氟哌噻吨可取代70 - 85%的结合）和饱和方式（最大结合容量Bmax值为65 - 176飞摩尔/毫克蛋白质）与基底神经节中的D1位点结合。特异性的125I-SCH 23982结合可被选择性D1拮抗剂SCH 23390（半数抑制浓度IC50 = 90皮摩尔）、顺式氟哌噻吨（IC50 = 200皮摩尔）和D1激动剂SKF 38393（IC50 = 110纳摩尔）取代，但不能被D2选择性配体（碘舒必利、LY 171555）或5-羟色胺拮抗剂西那色林取代。与3H-SCH 23390相比,125I-SCH 23982对D1位点的亲和力高5至10倍，比放射性高50倍，使其成为标记D1受体的优良放射性配体。D1位点的浓度在黑质内侧最高，比黑质外侧、尾壳核、伏隔核、嗅结节和内苍白球核中D1位点的浓度高出50%以上。内囊、背内侧额叶皮质、屏状核和新皮质第6层中D1位点的浓度较低。腹侧被盖区没有D1位点。纹状体内注射轴突保留神经毒素喹啉酸后，同侧尾壳核以及黑质内侧和中央网状部中可被取代的D1位点浓度分别降低了87%和46 - 58%。黑质外侧的D1位点没有减少。用6-羟基多巴胺破坏高达94%的中脑纹状体多巴胺能投射并没有降低D1结合，除了一个例外，也没有增加纹状体或黑质的D1受体浓度。125I-SCH 23982以皮摩尔亲和力选择性标记纹状体黑质神经元上的D1结合位点，这些神经元包含大鼠脑中大部分的D1位点。
