Loss of alpha-conotoxinMII- and A85380-sensitive nicotinic receptors in Parkinson's disease striatum.
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.
Quik
M
M
The Parkinson's Institute, Sunnyvale, California 94089, USA. mquik@thepi.org
Bordia
T
T
Forno
L
L
McIntosh
J M
JM
D000368:Aged; D000369:Aged, 80 and over; D001384:Azetidines / Q000494:pharmacology*; D020916:Conotoxins / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D011978:Receptors, Nicotinic / Q000378:metabolism*
C104288:A 85380; D001384:Azetidines; D020916:Conotoxins; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C098872:alpha-conotoxin MII