首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Loss of alpha-conotoxinMII- and A85380-sensitive nicotinic receptors in Parkinson's disease striatum
Authors:Quik M  Bordia T  Forno L  McIntosh J M
Institution:The Parkinson's Institute, Sunnyvale, California 94089, USA. mquik@thepi.org
Abstract:Multiple nicotinic receptors are present in rodent and monkey striatum, with a selective localization of alpha-conotoxinMII-sensitive sites in the striatum and preferential declines in their numbers after nigrostriatal damage. Here we report the presence of 125I-alpha-conotoxinMII and alpha-conotoxinMII-sensitive 125I-epibatidine nicotinic receptors in human control and Parkinson's disease striatum. 125I-alpha-ConotoxinMII bound to control striatum with the characteristics of a nicotinic receptor ligand although the number of sites was approximately fivefold lower than in rodent and monkey. Competition analyses of alpha-conotoxinMII with 125I-epibatidine showed that toxin-sensitive sites comprised approximately 15% of nicotinic receptors in human striatum. In Parkinson's disease caudate, there was a approximately 50% decline in 125I-alpha-conotoxinMII sites with a similar decline in the dopamine transporter. In putamen, there were substantially greater losses of the dopamine transporter (80-90%) but only 50-60% decreases in 125I-alpha-conotoxinMII sites with corresponding declines in alpha-conotoxinMII-sensitive 125I-epibatidine sites, 125I-epibatidine (multiple) sites and 125I-A85380 (beta2-containing) nicotinic receptors. The greater loss of the transporter compared with nicotinic sites suggests that only a subpopulation of nicotinic receptors is located pre-synaptically on striatal dopaminergic neurons in man. Correlation analyses between changes in nicotinic receptors and the dopamine transporter in Parkinson's disease striatum suggest that alpha-conotoxinMII-sensitive 125I-epibatidine sites (low-affinity sites), 125I-A85380 and 125I-epibatidine sites are localized in part to dopaminergic terminals. In summary, these results show that alpha-conotoxinMII-sensitive sites are present in human striatum and that there are high- and low-affinity subtypes which are both decreased in Parkinson's disease.
Keywords:A85380  caudate  dopamine transporter  epibatidine  nigrostriatal  putamen
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号