Sulfonylurea binding sites in normal human brain and in Parkinson's disease, progressive supranuclear palsy and Huntington's disease.
In human brain, [3H]glibenclamide binds with high affinity (KD about 3.5 nM) to sulfonylurea binding sites which are associated with ATP-sensitive potassium (KATP) channels. Regarding to the important neuromodulatory action of KATP channels in some neuronal populations, sulfonylurea binding sites were measured in several cortical areas (frontal and temporal cortex, hippocampus) and striatum (caudate nucleus and putamen) in controls and patients with Parkinson's disease or progressive supranuclear palsy. There was no modification of [3H]glibenclamide specific binding in the cerebral regions studied in both pathologies. These results indicate that KATP channels do not seem to be involved in the pathophysiology of these degenerative processes. Brain samples from five patients with Huntington's disease were studied. A small decrease in sulfonylurea binding sites was measured in the frontal cortex, caudate nucleus and putamen which could be due to the loss of either neurons or nerve endings. This low decrease contrasts with the dramatic diminution of many other markers associated with the profound striatal degeneration occurring in Huntington's disease.
Laboratoire de Neurochimie (C 1352), Université Catholique de Louvain, Brussels, Belgium.
S
S
Holemans
F
F
Javoy-Agid
Y
Y
Agid
F
F
De Paermentier
E C
EC
Laterre
J M
JM
Maloteaux
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D005905:Glyburide / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism*; D015221:Potassium Channels / Q000032:analysis* / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000032:analysis*; D012016:Reference Values; D064233:Sulfonylurea Receptors; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate; D005905:Glyburide