Reynolds D J, Lowenstein P R, Moorman J M, Grahame-Smith D G, Leslie R A
University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford.
Neurochem Int. 1994 Nov;25(5):455-64. doi: 10.1016/0197-0186(94)90022-1.
The distribution of muscarinic receptor binding was examined in the ferret brainstem vagal nuclei using the non-selective ligand [3H]quinuclidinyl benzilate and the relatively M1 receptor-selective ligand [3H]pirenzepine. The highest density of receptor sites are found in the subnucleus gelatinosus and lower levels in the other subnuclei of the nucleus of the tractus solitarius and in the area postrema and dorsal motor nucleus of the vagus nerve. Dense binding was also seen in the adjacent hypoglossal nucleus. Following unilateral cervical nodose ganglion excision binding in the subnucleus gelatinosus was attenuated ipsilateral to the lesion compared with the contralateral side. In contrast, [3H]pirenzepine binding was only seen in the subnucleus gelatinosus and in no other region at this level of the brainstem. This binding was reduced in the subnucleus as a whole by 52% ipsilateral to a cervical vagotomy. In the more rostral parts of the subnucleus gelatinosus, binding was undetectable ipsilateral to the lesion but more caudally, appreciable levels of binding persisted. This distribution parallels the known rostro-caudal variation in cross-over of vagal afferent fibres in the ferret dorsal vagal complex and indicates a presynaptic localization of [3H]pirenzepine binding sites on vagal afferent terminals. The distribution of binding of the high affinity choline uptake site blocker, [3H]hemicholinium-3, was also examined in the ferret brainstem using autoradiography. High densities of [3H]hemicholinium-3 binding were seen in the hypoglossal nucleus, the subnucleus gelatinosus and in the area postrema, with lower levels in the dorsal motor nucleus of the vagus, the trigeminal nucleus and other subnuclei of the nucleus of the tractus solitarius.(ABSTRACT TRUNCATED AT 250 WORDS)
利用非选择性配体[3H]奎宁环基苯甲酸酯和相对M1受体选择性配体[3H]哌仑西平,研究了雪貂脑干迷走神经核中毒蕈碱受体结合的分布情况。受体位点密度最高的区域位于胶状亚核,孤束核的其他亚核、最后区和迷走神经背运动核中的水平较低。在相邻的舌下神经核中也可见到密集结合。单侧颈结状神经节切除后,与对侧相比,胶状亚核中同侧病变部位的结合减弱。相比之下,[3H]哌仑西平结合仅见于胶状亚核,在脑干的这一水平上其他区域未见。在进行颈迷走神经切断术同侧,整个胶状亚核中的这种结合减少了52%。在胶状亚核更靠前的部分,病变同侧未检测到结合,但在更靠尾侧的部分,仍存在相当水平的结合。这种分布与雪貂背迷走神经复合体中迷走神经传入纤维交叉的已知头尾变化情况相似,表明[3H]哌仑西平结合位点位于迷走神经传入终末的突触前部位。还利用放射自显影术研究了高亲和力胆碱摄取位点阻滞剂[3H]半胱氨酸-3在雪貂脑干中的结合分布。在舌下神经核、胶状亚核和最后区可见到高密度的[3H]半胱氨酸-3结合,迷走神经背运动核、三叉神经核和孤束核的其他亚核中的水平较低。(摘要截短至250字)