Decreased brain [3H]inositol 1,4,5-trisphosphate binding in Alzheimer's disease.
Inositol 1,4,5-trisphosphate (IP3) receptor binding sites were studied in autopsied brains from 10 subjects with dementia of the Alzheimer type (DAT) and 10 age-matched controls. In the parietal cortex and hippocampus, there was a 50-70% loss of [3H]IP3 binding whereas no significant changes were observed in frontal, occipital and temporal cortices, caudate or amygdala. Scatchard analysis confirmed a reduction in receptor density rather than a change in affinity. Since muscarinic receptors are robustly coupled to IP3 formation, our data demonstrate abnormalities beyond the muscarinic receptor recognition site in DAT.
Young
L T
LT
Department of Psychiatry, University of Toronto, Clarke Institute of Psychiatry, Canada.
Kish
S J
SJ
Li
P P
PP
Warsh
J J
JJ
D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D015220:Calcium Channels; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D009928:Organ Specificity; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D013403:Sugar Phosphates / Q000378:metabolism*
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate