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Alpha and beta nicotinic acetylcholine receptors subunits and synaptophysin in putamen from Parkinson's disease

Lookup NU author(s): Dr Carmen Martin-Ruiz, Dr Margaret Piggott, Professor Alexander Mendelow, Dr Shahid Siddique, Emeritus Professor Robert Perry, Emeritus Professor Elaine Perry, Dr Jennifer Court

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Abstract

It is well established that nicotinic receptors in the mammalian striatum are involved in modulation of the release of several neurotransmitters, including dopamine. In addition, nicotinic receptors with high affinity for agonists have generally been found to be reduced in the striatum in Parkinson's disease. In the present study antibodies have been used to examine which subunits contribute to the striatal nicotinic receptor loss in Parkinson's disease, and whether the reduction in [3H]nicotine binding correlates with synaptic loss. Autopsy tissue from the putamen of 12 Parkinson's disease cases and 12 age-matched control subjects was analysed by immunoblotting using antibodies against recombinant peptides specific for α3, α4, α7, β2 and β4 nicotinic acetylcholine receptor (nAChR) subunits and the synaptic marker synaptophysin, in conjunction with assessment of [3H]nicotine binding by autoradiography. The data indicate that there is no loss of α3, α4, α7 and β2 immunoreactivity in the putamen in Parkinson's disease, despite a highly significant reduction in [3H]nicotine binding. An intense signal of β4 immunoreactivity was found in human dorsal root ganglia, but not in temporal cortex or putamen samples. Synaptophysin immunoreactivities were also similar in Parkinson's disease and control cases. These results suggest that the loss of nicotine binding in the putamen in Parkinson's disease may involve an nAChR subunit (e.g., α5 and/or α6) other than those investigated. Alternatively, the results could reflect impaired subunit assembly at the plasma membrane. Copyright (C) 2000 Elsevier Science Ltd.


Publication metadata

Author(s): Martin-Ruiz CM, Piggott M, Gotti C, Lindstrom J, Mendelow AD, Siddique MS, Perry RH, Perry EK, Court JA

Publication type: Review

Publication status: Published

Journal: Neuropharmacology

Year: 2000

Volume: 39

Issue: 13

Pages: 2830-2839

Print publication date: 01/01/2000

ISSN (print): 0028-3908

ISSN (electronic): 1873-7064

URL: http://dx.doi.org/10.1016/S0028-3908(00)00110-6

DOI: 10.1016/S0028-3908(00)00110-6

PubMed id: 11044753


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