Laruelle M, Vanisberg M A, Maloteaux J M
Service de Psychiatrie, Université Catholique de Louvain, Brussels, Belgium.
Biol Psychiatry. 1988 Jul;24(3):299-309. doi: 10.1016/0006-3223(88)90198-9.
The characteristics of the binding of [3H]paroxetine, a selective serotonin (5-HT) uptake blocker, were investigated in human brain. The Kd value was 0.23 +/- 0.07 nM, and the Bmax value was 190 +/- 39 fmol/mg protein in the putamen. The capacity of various antidepressive drugs to inhibit [3H]paroxetine-specific binding in human brain was well correlated with their capacity to inhibit [3H]5-HT uptake in rat brain. The highest concentrations of [3H]paroxetine-specific binding sites were found in the substantia nigra, hypothalamus, and hippocampus. Lower values were obtained in the basal ganglia and the thalamus. The specific binding was very low in cerebral and cerebellar cortices. The regional distribution of [3H]paroxetine binding sites differs from that of [3H]ketanserin binding to S2 serotonin receptors. The subcellular distribution of the [3H]paroxetine-specific binding sites obtained by differential centrifugation revealed a synaptosomal enrichment in the frontal cortex and striatum, whereas an enrichment in the microsomal fraction was found in striatum. The results show that [3H]paroxetine is a ligand of choice to label the 5-HT uptake molecular complex in human brain.
在人脑组织中研究了选择性5-羟色胺（5-HT）摄取阻滞剂[3H]帕罗西汀的结合特性。壳核中的解离常数（Kd）值为0.23±0.07nM，最大结合容量（Bmax）值为190±39fmol/mg蛋白。多种抗抑郁药物抑制人脑组织中[3H]帕罗西汀特异性结合的能力，与其抑制大鼠脑组织中[3H]5-HT摄取的能力密切相关。[3H]帕罗西汀特异性结合位点浓度最高的脑区为黑质、下丘脑和海马。基底神经节和丘脑的结合位点浓度较低。大脑皮质和小脑皮质的特异性结合水平很低。[3H]帕罗西汀结合位点的区域分布与[3H]酮色林与5-HT2受体的结合位点分布不同。通过差速离心法得到的[3H]帕罗西汀特异性结合位点的亚细胞分布显示，额叶皮质和纹状体中突触体部分结合位点富集，而纹状体中微粒体部分结合位点富集。结果表明，[3H]帕罗西汀是标记人脑5-HT摄取分子复合物的理想配体。
