Loss of cortical GABA uptake sites in Alzheimer's disease.
[3H]Nipecotic acid bound to membranes of human brain in a saturable, reversible manner which was totally dependent on the presence of sodium ions. The potencies of compounds in inhibiting the specific binding of [3H]nipecotic acid were closely correlated with their potencies in inhibiting the neuronal uptake of [3H]GABA. Compounds selective for GABA receptors were inactive. [3H]Nipecotic acid appears to label neuronal high affinity GABA uptake sites. The binding of [3H]nipecotic acid was substantially reduced in the temporal cortex of brains from subjects with Alzheimer-type dementia, but not in other brain regions. It is concluded that some loss of GABA terminals occurs in this disease.
Simpson
M D
MD
Department of Physiological Sciences, University of Manchester, U.K.
Cross
A J
AJ
Slater
P
P
Deakin
J F
JF
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009557:Nipecotic Acids / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009557:Nipecotic Acids; D011963:Receptors, GABA-A; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; D011392:Proline; C010983:homoproline