Codd E E, Shank R P
Drug Discovery Research, R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Eur J Pharmacol. 1992 Jul 7;217(2-3):149-52. doi: 10.1016/0014-2999(92)90837-t.
Studies of 1,3-di-(2-[5-3H]tolyl)guanidine ([3H]DTG) binding to rat brain membranes revealed that [3H]DTG binds to a high and a low affinity site with Kd values of 19.8 nM and 1.31 microM (corresponding Bmax values 291 fmol/mg protein and 8.68 pmol/mg protein). The order of potency of competitors for [3H]DTG binding revealed a binding profile typical of sigma site ligands. Several sigma ligands such as the enantiomers of 3-PPP (3-(3-hydroxyphenyl)-N- (n-propyl)piperidine) and (+/-)-pentazocine exhibited biphasic competition profiles for [3H]DTG binding, whereas other sigma ligands such as haloperidol displayed monotonic competition curves. Neither phenytoin nor carbamazepine were observed to enhance [3H]DTG binding. These data support the hypothesis that multiple sigma binding sites exist. The lack of phenytoin and carbamazepine modulation of [3H]DTG binding are in agreement with the proposed greater density of sigma site 2 in the rat, since allosteric modulation has been ascribed to the DM1/sigma 1 site.
对1,3 - 二 -（2 - [5 - ³H]甲苯基）胍（[³H]DTG）与大鼠脑膜结合的研究表明，[³H]DTG与一个高亲和力位点和一个低亲和力位点结合，其解离常数（Kd）值分别为19.8 nM和1.31 μM（相应的最大结合量（Bmax）值分别为291 fmol/mg蛋白质和8.68 pmol/mg蛋白质）。[³H]DTG结合竞争剂的效力顺序显示出典型的σ位点配体结合特征。几种σ配体，如3 - PPP（3 -（3 - 羟基苯基）- N -（正丙基）哌啶）的对映体和（±）-喷他佐辛，对[³H]DTG结合表现出双相竞争曲线，而其他σ配体，如氟哌啶醇，则显示出单调竞争曲线。未观察到苯妥英和卡马西平增强[³H]DTG结合。这些数据支持存在多个σ结合位点的假说。苯妥英和卡马西平对[³H]DTG结合缺乏调节作用，这与大鼠中σ位点2密度更高的提议一致，因为变构调节已归因于DM1/σ1位点。
