PRESERVATION OF ACETYLCHOLINE MUSCARINIC M2 RECEPTOR G-PROTEIN INTERACTIONS IN THE NEOCORTEX OF PATIENTS WITH ALZHEIMERS-DISEASE

The efficacy of acetylcholine muscarinic M2 receptor-G-protein couplin g was investigated in Alzheimer's disease and control neocortical memb ranes by measuring the effects of MgCl2 and 5'-guanylylimidodiphosphat e (Gpp[NH]p) on high-affinity [H-3]oxotremorine-M ([H-3]OXO-M) binding . MgCl2 gave similar enhancements of [H-3]OXO-M binding in Alzheimer's disease and control occipital cortex. In contrast, MgCl2 enhanced [H- 3]OXO-M binding was significantly higher in Alzheimer's disease superi or temporal cortex, compared to controls. MgCl2 enhanced [H-3]OXO-M bi nding in both the occipital and temporal cortices of the Alzheimer's d isease cases was reversed to control levels by Gpp[NH]p. It is conclud ed that the number of high-affinity muscarinic M2 sites is increased i n Alzheimer's disease superior temporal, but not occipital, cortex and that M2 sites in both regions maintain an efficient G-protein couplin g.