Ransom R W, Asarch K B, Shih J C
J Neurochem. 1985 Mar;44(3):875-80. doi: 10.1111/j.1471-4159.1985.tb12897.x.
The inhibition of [3H]5-hydroxytryptamine [( 3H]5-HT) binding in rat brain by 1-[2-(3-bromoacetamidophenyl)ethyl]-4-(3-trifluoromethylphenyl) piperazine (BrAcTFMPP) and that by spiperone were compared. Spiperone inhibition of [3H]5-HT binding in cortex was consistent with displacement from two sites with dissociation constants (KD) of 24 nM (5-HT-1A site) and 19 microM (5-HT-1B site) for spiperone. BrAcTFMPP also discriminated two subpopulations of [3H]5-HT binding sites with dissociation constants of 0.5 nM and 146 nM for the compound. The proportion of high-affinity sites for each compound represented about 35% of the specific [3H]5-HT binding. In the presence of 1 microM spiperone, a concentration that saturates the 5-HT-1A sites while having a minimal effect on 5-HT-1B sites, BrAcTFMPP displaced [3H]5-HT from a single site with a KD for BrAcTFMPP of 145 nM. The inhibition of [3H]5-HT binding by spiperone in the presence of 30 nM BrAcTFMPP was best fit by a single-site model with a KD of 21 microM for spiperone. In corpus striatum, 5-HT-1A sites, as defined with spiperone, represented 15% of the specific [3H]5-HT binding and 30 nM BrAcTFMPP also blocked about 15% of the binding. A significant difference between spiperone and BrAcTFMPP was their affinity for 5-HT-2 receptors. BrAcTFMPP (KD = 41 nM) had an 80-fold lower affinity for these sites than spiperone (KD = 0.5 nM). Thus, BrAcTFMPP and spiperone discriminate the same two subpopulations of [3H]5-HT binding sites and BrAcTFMPP displays a high affinity and a selectivity for 5-HT-1A sites versus both 5-HT-1B and 5-HT-2 sites.
比较了1-[2-(3-溴乙酰氨基苯基)乙基]-4-(3-三氟甲基苯基)哌嗪(BrAcTFMPP)和螺哌隆对大鼠脑内[3H]5-羟色胺([3H]5-HT)结合的抑制作用。螺哌隆对皮质中[3H]5-HT结合的抑制作用与从两个位点的置换一致，螺哌隆的解离常数(KD)分别为24 nM(5-HT-1A位点)和19 μM(5-HT-1B位点)。BrAcTFMPP也区分了[3H]5-HT结合位点的两个亚群，该化合物的解离常数分别为0.5 nM和146 nM。每种化合物的高亲和力位点比例约占特异性[3H]5-HT结合的35%。在1 μM螺哌隆存在下，该浓度使5-HT-1A位点饱和，而对5-HT-1B位点影响最小，BrAcTFMPP从单个位点置换[3H]5-HT，BrAcTFMPP的KD为145 nM。在30 nM BrAcTFMPP存在下，螺哌隆对[3H]5-HT结合的抑制作用最适合用单一位点模型拟合，螺哌隆的KD为21 μM。在纹状体中，用螺哌隆定义的5-HT-1A位点占特异性[3H]5-HT结合的15%，30 nM BrAcTFMPP也阻断了约15%的结合。螺哌隆和BrAcTFMPP之间的一个显著差异是它们对5-HT-2受体的亲和力。BrAcTFMPP(KD = 41 nM)对这些位点的亲和力比螺哌隆(KD = 0.5 nM)低80倍。因此，BrAcTFMPP和螺哌隆区分了相同的两个[3H]5-HT结合位点亚群，并且BrAcTFMPP对5-HT-1A位点相对于5-HT-1B和5-HT-2位点均表现出高亲和力和选择性。
