Autoradiographic localization of [3H]dextromethorphan in guinea pig brain: allosteric enhancement by ropizine.
Autoradiographic localization of [3H]dextromethorphan in guinea pig brain: allosteric enhancement by ropizine.
复制标题
[3H]右美沙芬在豚鼠脑中的放射自显影定位：罗匹嗪的变构增强。
DOI：
10.1002/jnr.490240224
复制
发表时间：
1989
影响因子：
4.2
通讯作者：
Musacchio,JM
中科院分区：
文献类型：
--
作者：
Canoll,PD;Smith,PR;Gottesman,S;Musacchio,JM
右美沙芬 (DM) 是一种具有抗惊厥活性的镇咳药，可与豚鼠脑匀浆中的高亲和力和低亲和力位点结合。我们使用抗惊厥药罗匹嗪（一种降低 [3 H] DM 解离速率的变构调节剂）检查了 [3 H] DM 的放射自显影定位。竞争研究表明，与脑切片的结合与脑匀浆的结合相同 [Craviso 和 Musacchio: Mol Pharmacol 23: 629–640, 1983b]。对放射自显影图像的计算机辅助定量分析表明，[3 H]DM 与整个大脑的离散结构结合，但在中脑、脑桥和延髓中密度较高。在横纹肌样核、中缝背核、中缝核、尾部线性中缝核和颅运动神经核中观察到最强烈的标记。中央灰色在其整个头尾范围内显示出中度至高密度的标记，在背侧被盖核和蓝斑中具有非常高的结合。在几个下丘脑结构中也观察到中度和高度结合。在梨状皮质的锥体细胞层、压后皮质、齿状回的颗粒细胞层、海马的锥体细胞层和小脑的浦肯野细胞层中看到明显的中度结合带。 [3 H] DM 和 sigma 配体的结合分布之间的惊人相似性，加上脑匀浆中的竞争研究，支持了 DM 和 sigma 配体共享共同的高亲和力结合位点的假设 [Musacchio 等人：Mol Pharmacol 35: 1-5, 1989]。 [3 H] DM 结合的分布为 DM 的镇咳和抗惊厥作用提供了可能的解剖学基础。
Dextromethorphan (DM) is an antitussive with anticonvulsant activity that binds to high-and low-affinity sites in guinea pig brain homogenates. We examined the autoradiographic localization of [3 H] DM using the anticonvulsant ropizine, an allosteric modifier that decreases the dissociation rate of [3 H] DM. Competition studies demonstrated that the binding to brain sections was identical to that of brain homogenates [Craviso and Musacchio: Mol Pharmacol 23: 629–640, 1983b]. Computer-assisted quantitative analysis of the autoradiographic images demonstrated that [3 H] DM binds to discrete structures throughout the brain, but with higher density in the midbrain, pons, and medulla oblongata. The most intense labeling was observed in the rhabdoid, dorsal raphe, median raphe, caudal linear raphe nuclei, and cranial motor nerve nuclei. The central gray showed moderate to high-density labeling throughout its entire rostro-caudal extent, with very high binding in the dorsal tegmental nucleus and the locus coeruleus. Moderate and high binding was also seen in several hypothalamic structures. Distinct bands of moderate binding were seen in the pyramidal cell layer of the piriform cortex, the retrosplenial cortex, the granular cell layer of the dentate gyrus, the pyramidal cell layer of the hippocampus, and the Purkinje cell layer of the cerebellum. The striking similarity between the binding distribution of [3 H] DM and sigma ligands, plus competition studies in brain homogenate, support the hypothesis that DM and sigma ligands share a common highaffinity binding site [Musacchio et al: Mol Pharmacol 35: 1–5, 1989]. The distribution of [3 H] DM binding provides possible anatomical substrates for both the antitussive and anticonvulsant actions of DM.