Abstract
The effect of Alzheimer's disease (AD) on the activity of the phosphoinositide second messenger system was studied by measuring the hydrolysis of [3H]phosphatidylinositol (PI) by membranes from postmortem human prefrontal cortex. The activity of phospholipase C was similar in AD and control tissue. Activation with GTPγS and with carbachol demonstrated less [3H]PI hydrolysis in AD than control membranes. The concentration of Gq/11, the G-proteins most likely functional in phosphoinositide metabolism, was unchanged in AD compared with controls, indicating that function of the receptor-G-protein complex rather than the G-protein concentration was the site of the impairment in AD. These results indicate that postsynaptic muscarinic receptor responses are impaired in AD, a finding that may explain, in part, the limited therapeutic responses achieved by administration of cholinomimetics to patients with AD. Also, this assay provides a means to identify cholinomimetics that are most effective in activating muscarinic receptor-coupled phosphoinositide hydrolysis in human brain, agents which should have the greatest potential for providing therapeutic responses in AD.
Original language | English (US) |
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Pages (from-to) | 221-226 |
Number of pages | 6 |
Journal | Neurobiology of aging |
Volume | 15 |
Issue number | 2 |
DOIs | |
State | Published - Jan 1 1994 |
Externally published | Yes |
Keywords
- Alzheimer's disease
- Cholinergic receptor
- G-proteins
- Human brain
- Phosphoinositide hydrolysis
ASJC Scopus subject areas
- Clinical Neurology
- Biological Psychiatry
- Developmental Neuroscience
- Neurology
- Psychology(all)