Preservation of acetylcholine muscarinic M2 receptor G-protein interactions in the neocortex of patients with Alzheimer's disease.
The efficacy of acetylcholine muscarinic M2 receptor-G protein coupling was investigated in Alzheimer's disease and control neocortical membranes by measuring the effects of MgCl2 and 5'-guanylylimidodiphosphate (Gpp[NH]p) on high-affinity [3H]oxotremorine-M ([3H]OXO-M) binding. MgCl2 gave similar enhancements of [3H]OXO-M binding in Alzheimer's disease and control occipital cortex. In contrast, MgCl2 enhanced [3H]OXO-M binding was significantly higher in Alzheimer's disease superior temporal cortex, compared to controls. MgCl2 enhanced [3H]OXO-M binding in both the occipital and temporal cortices of the Alzheimer's disease cases was reversed to control levels by Gpp[NH]p. It is concluded that the number of high-affinity muscarinic M2 sites is increased in Alzheimer's disease superior temporal, but not occipital, cortex and that M2 sites in both regions maintain an efficient G-protein coupling.
Hérnandez-Hérnandez
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Department of Biochemistry and Molecular Biology, University of Salamanca, Spain.
Adem
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A
Ravid
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Cowburn
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RF
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D018727:Muscarinic Antagonists; D010095:Oxotremorine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D006165:Guanylyl Imidodiphosphate; D010095:Oxotremorine; D019204:GTP-Binding Proteins