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 GTP gamma S 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.
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Authors | R S Jope, L Song, X Li, R Powers |
Journal | Neurobiology of aging
(Neurobiol Aging)
1994 Mar-Apr
Vol. 15
Issue 2
Pg. 221-6
ISSN: 0197-4580 [Print] United States |
PMID | 7838295
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Muscarinic Agonists
- Phosphatidylinositols
- Receptors, Muscarinic
- Guanosine 5'-O-(3-Thiotriphosphate)
- Carbachol
- Type C Phospholipases
- GTP-Binding Proteins
- Calcium
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Topics |
- Aged
- Alzheimer Disease
(enzymology, metabolism)
- Blotting, Western
- Brain Chemistry
(drug effects, physiology)
- Calcium
(metabolism)
- Carbachol
(pharmacology)
- GTP-Binding Proteins
(metabolism)
- Guanosine 5'-O-(3-Thiotriphosphate)
(metabolism)
- Humans
- Hydrogen-Ion Concentration
- Hydrolysis
- In Vitro Techniques
- Muscarinic Agonists
(pharmacology)
- Phosphatidylinositols
(metabolism)
- Receptors, Muscarinic
(drug effects, metabolism)
- Type C Phospholipases
(metabolism)
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