Alpha and beta nicotinic acetylcholine receptors subunits and synaptophysin in putamen from Parkinson's disease.
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.
Martin-Ruiz
C M
CM
Joint MRC Newcastle University Centre Development for Clinical Brain Aging, MRC Building, Newcastle General Hospital, Westgate Road, NE4 6BE, Newcastle upon Tyne, UK.
Piggott
M
M
Gotti
C
C
Lindstrom
J
J
Mendelow
A D
AD
Siddique
M S
MS
Perry
R H
RH
Perry
E K
EK
Court
J A
JA
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001345:Autoradiography; D015153:Blotting, Western; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009538:Nicotine / Q000378:metabolism; D018722:Nicotinic Agonists / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism*
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D016708:Synaptophysin; D009538:Nicotine