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 [(3)H]
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 alpha3, alpha4, alpha7, beta2 and beta4
nicotinic acetylcholine receptor (nAChR) subunits and the synaptic marker
synaptophysin, in conjunction with assessment of [(3)H]
nicotine binding by autoradiography. The data indicate that there is no loss of alpha3, alpha4, alpha7 and beta2 immunoreactivity in the putamen in
Parkinson's disease, despite a highly significant reduction in [(3)H]
nicotine binding. An intense signal of beta4 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., alpha5 and/or alpha6) other than those investigated. Alternatively, the results could reflect impaired subunit assembly at the plasma membrane.