Hemstreet M K, Matsumoto R R, Bowen W D, Walker J M
Department of Neuroscience, Brown University, Providence, RI 02912.
Brain Res. 1993 Nov 12;627(2):291-8. doi: 10.1016/0006-8993(93)90333-i.
The relationship between sigma binding and the behavioral efficacy of a selective sigma ligand was examined in rats of varying ages (30, 45, 60, 75, 90, and 150 days old). Scatchard analyses of the binding of the sigma radioligand [3H]1,3-di-o-tolylguanidine ([3H]DTG) to brain membranes revealed significant age-related differences in binding to both crude synaptosomal and microsomal fractions. The functional significance of these developmental changes in sigma ligand binding was studied by determining the postural effects of rubral microinjections of DTG in age-matched littermates of rats used in the binding studies. The degree of dystonia produced by a single dose of DTG was significantly correlated with the amount of [3H]DTG bound to rat brain synaptosomal membranes at low but not at high concentrations. No significant correlation between binding to the microsomal fraction and drug efficacy was observed. These experimental results were in good agreement with predicted amounts bound as estimated from a Scatchard analysis of the data. The results suggest that sigma binding sites found in brain synaptosomal membranes are functional receptors involved in the control of movement and posture.
在不同年龄（30、45、60、75、90和150日龄）的大鼠中研究了σ结合与选择性σ配体行为效力之间的关系。对σ放射性配体[³H]1,3-二邻甲苯基胍（[³H]DTG）与脑膜结合进行Scatchard分析，结果显示，其与粗制突触体和微粒体组分的结合存在显著的年龄相关差异。通过在结合研究中使用的大鼠的年龄匹配同窝仔鼠中，测定红核微量注射DTG后的姿势效应，研究了这些σ配体结合发育变化的功能意义。单剂量DTG产生的肌张力障碍程度与低浓度而非高浓度下与大鼠脑突触体膜结合的[³H]DTG量显著相关。未观察到与微粒体组分的结合与药物效力之间存在显著相关性。这些实验结果与根据数据的Scatchard分析估计的预测结合量高度一致。结果表明，在脑突触体膜中发现的σ结合位点是参与运动和姿势控制的功能性受体。
