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ABSTRACT: Loss of -conotoxinMII- and A85380-sensitive nicotinic receptors in Parkinson's disease striatum M. Quik*, T. Bordia*, L. Forno and J. M. McIntosh * The Parkinson's Institute, Sunnyvale, California, USA VA Palo Alto Health Care System, Palo Alto, California, USA Department of Biology and Psychiatry, University Utah, Salt Lake City, Utah, USA Address correspondence and reprint requests to Maryka Quik, The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, CA 94089, USA. E-mail: [log in to unmask] Multiple nicotinic receptors are present in rodent and monkey striatum, with a selective localization of -conotoxinMII- sensitive sites in the striatum and preferential declines in their numbers after nigrostriatal damage. Here we report the presence of 125I--conotoxinMII and -conotoxinMII-sensitive 125I-epibatidine nicotinic receptors in human control and Parkinson's disease striatum. 125I--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 -conotoxinMII with 125I-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 125I--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--conotoxinMII sites with corresponding declines in -conotoxinMII-sensitive 125I-epibatidine sites, 125I-epibatidine (multiple) sites and 125I-A85380 (ß2-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 -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 -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. Key Words: A85380 – caudate – dopamine transporter – epibatidine – nigrostriatal – putamen Abbreviations used: 125I-RTI-121, 3ß-(4-[125I]iodophenyl)tropane-2ß-carboxylic acid isopropyl ester SOURCE: Journal of Neurochemistry, Vol. 88, No. 3, 2004 668-679 http://www.jneurochem.org/cgi/content/abstract/88/3/668 * * * ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn