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.