Tejani-Butt S M
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia.
J Pharmacol Exp Ther. 1992 Jan;260(1):427-36.
The uptake sites for norepinephrine (NE) in brain have not been studied in much detail, probably due to the absence of an adequate radioligand for labeling these sites. This study describes the binding properties of [3H]nisoxetine to uptake sites for NE in rat brain homogenates and in tissue slices analyzed by quantitative autoradiography. The binding of [3H]nisoxetine was found to be saturable and sodium-dependent to a single class of binding sites (Kd = 0.8 nM). The potencies of drugs to inhibit the uptake of NE correlated highly with their potencies to inhibit the binding of [3H]nisoxetine. Studies using [3H]nisoxetine for mapping of sites associated with uptake of NE by quantitative autoradiography indicated that the pattern of binding of [3H] nisoxetine is consistent with the pattern of noradrenergic innervation. Destruction of central noradrenergic neurons by 6-OH-dopamine or DSP-4 resulted in large decreases in the binding of [3H]nisoxetine in almost all areas of the brain regions examined. [3H]Nisoxetine should prove to be a useful tool to study the regulation of uptake sites for NE as well as a useful marker for noradrenergic innervation in the study of various neurological diseases.
脑中去甲肾上腺素（NE）的摄取位点尚未得到详细研究，这可能是由于缺乏用于标记这些位点的合适放射性配体。本研究描述了[3H]尼索西汀与大鼠脑匀浆及通过定量放射自显影分析的组织切片中NE摄取位点的结合特性。发现[3H]尼索西汀与一类结合位点的结合具有饱和性且依赖于钠离子（解离常数Kd = 0.8 nM）。药物抑制NE摄取的效力与其抑制[3H]尼索西汀结合的效力高度相关。使用[3H]尼索西汀通过定量放射自显影绘制与NE摄取相关位点的研究表明，[3H]尼索西汀的结合模式与去甲肾上腺素能神经支配模式一致。用6-羟基多巴胺或DSP-4破坏中枢去甲肾上腺素能神经元导致在所检查的几乎所有脑区中[3H]尼索西汀的结合大幅减少。[3H]尼索西汀应被证明是研究NE摄取位点调节的有用工具，也是研究各种神经疾病中去甲肾上腺素能神经支配的有用标记物。
