List S J, Seeman P
Proc Natl Acad Sci U S A. 1981 Apr;78(4):2620-4. doi: 10.1073/pnas.78.4.2620.
A procedure was developed to identify receptors for dopamine and serotonin separately and selectively by means of [3H]spiperone and to measure the density of each receptor in different regions of the rat brain. In the striatum, the binding of [3H]spiperone to dopamine receptors was inhibited by sulpiride but not by quinazolinedone R43448 (R43448); in the frontal cortex, however, the binding of [3H]spiperone to serotonin receptors was inhibited by R43448 but not by sulpiride. Thus, the density of dopamine receptors (D2 sites) was measured by [3H]spiperone binding in the presence of 0.1 microM R43448 (to preclude the attachment of the 3H-labeled ligand to serotonin sites), while the density of serotonin receptors (S2 sites) was measured by [3H]spiperone binding in the presence of 10 microM sulpiride (to preclude the attachment of the 3H-labeled ligand to dopamine sites). The density of D2 sites was highest in the striatum, followed by the olfactory tubercle, hypothalamus, substantia nigra, and the lower pons--medulla region. All five regions had similar dissociation constants (Kd values) of 0.05--0.15 nM. The density of S2 sites was highest in the frontal cortex, followed by the posterior cortex, olfactory tubercle, striatum, hypothalamus, and thalamus, and all regions had Kd values in the range 0.6--2.3 nM. Thus, because the Kd values were similar for all regions, and because Scatchard analyses revealed a single set of sites for either D2 or S2 (where detected), the main criteria for resolving the dopamine and serotonin components of [3H]spiperone binding were considered fulfilled.
已开发出一种程序，可借助[³H]螺哌隆分别且选择性地鉴定多巴胺和5-羟色胺的受体，并测量大鼠脑不同区域中每种受体的密度。在纹状体中，[³H]螺哌隆与多巴胺受体的结合可被舒必利抑制，但不受喹唑啉酮R43448（R43448）抑制；然而，在额叶皮质中，[³H]螺哌隆与5-羟色胺受体的结合可被R43448抑制，但不受舒必利抑制。因此，多巴胺受体（D2位点）的密度通过在0.1微摩尔R43448存在下的[³H]螺哌隆结合来测量（以防止³H标记配体与5-羟色胺位点结合），而5-羟色胺受体（S2位点）的密度通过在10微摩尔舒必利存在下的[³H]螺哌隆结合来测量（以防止³H标记配体与多巴胺位点结合）。D2位点的密度在纹状体中最高，其次是嗅结节、下丘脑、黑质以及脑桥下部 - 延髓区域。所有这五个区域的解离常数（Kd值）相似，为0.05 - 0.15纳摩尔。S2位点的密度在额叶皮质中最高，其次是后皮质、嗅结节、纹状体、下丘脑和丘脑，并且所有区域的Kd值在0.6 - 2.3纳摩尔范围内。因此，由于所有区域的Kd值相似，并且由于Scatchard分析显示对于检测到的D2或S2（无论检测到哪种）均为单一的位点集，所以认为满足解析[³H]螺哌隆结合的多巴胺和5-羟色胺成分的主要标准。
