Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, Scotland (UK).
Restor Neurol Neurosci. 1992 Jan 1;3(6):293-300. doi: 10.3233/RNN-1992-3602.
The pharmacological characteristics of both muscarinic receptors and high-affinity choline uptake sites were examined within intracerebral implants of foetal basal forebrain cell suspensions. Approximately 12 weeks after implantation, the transplants were identified by acetylcholinesterase histochemistry. Muscarinic receptors were labelled by [3H]quinuclidinyl benzylate (QNB) autoradiography. The M1 and M2 receptor components of QNB binding were differentiated by pirenzepine competition. The distribution of the high-affinity choline uptake site was examined using [3H]hemicholinium-3 (HC3) autoradiography. Unilateral lesion of the nucleus basalis reduced [3H]QNB (8-25%) and [3H]HC3 (19-43%) binding throughout host frontoparietal cortex ipsilateral to the lesion but did not significantly alter these cholinergic markers within cingulate cortex, subcortical white matter, striatum or septum. Saturation analysis of the implanted tissue revealed the presence of a single population of [3H]QNB and [3H]HC3 binding sites with affinities similar to those of the host tissue (KD = 0.43 nM and 20.4 nM respectively). However, the receptor profile which developed appeared to be intrinsic to the implant; it was unaffected by the site of implantation and was dissimilar to that which ultimately developed in the donor tissue when left in situ.
在胎脑基底前脑细胞悬浮液的脑内植入物中,检查了毒蕈碱受体和高亲和力胆碱摄取位点的药理学特征。植入后约 12 周,通过乙酰胆碱酯酶组织化学鉴定移植体。用[3H]奎宁环苯酯(QNB)放射自显影标记毒蕈碱受体。通过哌仑西平竞争区分 QNB 结合的 M1 和 M2 受体成分。使用[3H]半胆碱-3(HC3)放射自显影研究高亲和力胆碱摄取位点的分布。基底核单侧损伤减少了宿主额顶叶皮质对损伤侧的[3H]QNB(8-25%)和[3H]HC3(19-43%)结合,但对扣带回皮质、皮质下白质、纹状体或隔区的这些胆碱能标记物没有显著影响。植入组织的饱和分析显示存在与宿主组织相似亲和力的单一[3H]QNB 和[3H]HC3 结合位点群体(KD 分别为 0.43 nM 和 20.4 nM)。然而,所发展的受体谱似乎是植入物的固有特性;它不受植入部位的影响,与原位保留时供体组织最终发展的受体谱不同。