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Loss of α‐conotoxinMII‐ and A85380‐sensitive nicotinic receptors in Parkinson's disease striatum
Author(s) -
Quik M.,
Bordia T.,
Forno L.,
McIntosh J. M.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02177.x
Subject(s) - epibatidine , nicotinic agonist , dopaminergic , striatum , putamen , dopamine transporter , dopamine , biology , endocrinology , receptor , medicine , neuroscience , chemistry , nicotinic acetylcholine receptor , biochemistry
Multiple nicotinic receptors are present in rodent and monkey striatum, with a selective localization of α‐conotoxinMII‐sensitive sites in the striatum and preferential declines in their numbers after nigrostriatal damage. Here we report the presence of 125 I‐α‐conotoxinMII and α‐conotoxinMII‐sensitive 125 I‐epibatidine nicotinic receptors in human control and Parkinson's disease striatum. 125 I‐α‐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 α‐conotoxinMII with 125 I‐epibatidine showed that toxin‐sensitive sites comprised ≈15% of nicotinic receptors in human striatum. In Parkinson's disease caudate, there was a ≈50% decline in 125 I‐α‐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 125 I‐α‐conotoxinMII sites with corresponding declines in α‐conotoxinMII‐sensitive 125 I‐epibatidine sites, 125 I‐epibatidine (multiple) sites and 125 I‐A85380 (β2‐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 α‐conotoxinMII‐sensitive 125 I‐epibatidine sites (low‐affinity sites), 125 I‐A85380 and 125 I‐epibatidine sites are localized in part to dopaminergic terminals. In summary, these results show that α‐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.