Barnes J M, Barnes N M, Barber P C, Champaneria S, Costall B, Hornsby C D, Ironside J W, Naylor R J
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, UK.
Naunyn Schmiedebergs Arch Pharmacol. 1992 Feb;345(2):197-202. doi: 10.1007/BF00165736.
The radioligand binding characteristics of [3H]haloperidol (in the presence of spiperone, 25 nmolL-1) were investigated in rat and human cerebellar membranes. In both rat and human cerebellar membrane preparations saturation studies with [3H]haloperidol (non-specific binding defined by pentazocine, 10 mumolsL-1) demonstrated high affinity saturable specific binding to a homogenous population of binding sites (rat, Bmax 6693 +/- 1242 fmol mg-1 protein, pKD 8.33 +/- 0.08; human, Bmax 2550 +/- 437 fmol mg-1 protein, pKD 8.59 +/- 0.11; mean +/- SEM, n = 3-6). Competition studies employing a wide range of structurally diverse competing compounds displayed that the [3H]haloperidol binding site was pharmacologically similar in both preparations and comparable to sigma recognition sites previously identified in various tissues originating from different species. In addition, with reference to the potential subtypes of sigma recognition sites, the labelling of these sites by low nanomolar concentrations of [3H]haloperidol provides evidence that they belong to the sigma-1 recognition site subtype. The present findings suggest that the pharmacology of the rat and human cerebellar sigma recognition site are directly comparable and provides further supporting evidence towards the use of [3H]haloperidol radioligand binding studies in the rat to detect sigma receptor ligands with potential therapeutic activity.
在大鼠和人类小脑膜中研究了[3H]氟哌啶醇（在存在螺哌隆，25 nmol/L的情况下）的放射性配体结合特性。在大鼠和人类小脑膜制剂中，用[3H]氟哌啶醇进行饱和研究（非特异性结合由喷他佐辛定义，10 μmol/L）表明，与同质的结合位点群体存在高亲和力的可饱和特异性结合（大鼠，Bmax 6693±1242 fmol mg-1蛋白质，pKD 8.33±0.08；人类，Bmax 2550±437 fmol mg-1蛋白质，pKD 8.59±0.11；平均值±SEM，n = 3 - 6）。使用多种结构不同的竞争化合物进行的竞争研究显示，[3H]氟哌啶醇结合位点在两种制剂中的药理学性质相似，并且与先前在源自不同物种的各种组织中鉴定的σ识别位点相当。此外，关于σ识别位点的潜在亚型，低纳摩尔浓度的[3H]氟哌啶醇对这些位点的标记提供了证据，表明它们属于σ-1识别位点亚型。目前的研究结果表明，大鼠和人类小脑σ识别位点的药理学性质直接可比，并为在大鼠中使用[3H]氟哌啶醇放射性配体结合研究来检测具有潜在治疗活性的σ受体配体提供了进一步的支持证据。
