title: Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients.
abstract: We assessed muscarinic M(1), M(2) and M(4) receptor subtypes in the hippocampus of Alzheimer's and control brains by receptor autoradiography using ligands such as [(125)I]muscarinic toxin-1 ([(125)I]MT-1, M(1) selective), [(3)H]AFDX-384 (M(2) partially selective) and [(125)I]muscarinic toxin 4 ([(125)I]M(4) toxin-1, M(4) selective). Our results revealed a significant decrease in muscarinic M(4) receptor binding in the dentate gyrus and CA4 regions of brain sections from Alzheimer's patients compared to controls. No changes in the density of M(1) or M(2) receptor binding were observed. Our findings suggest that, relative to other muscarinic receptor subtypes, the M(4) receptor could be the subtype which is selectively compromised in Alzeheimer's disease (AD).
authors.affiliation: Department of Clinical Neuroscience (NEUROTEC), Section of Experimental Geriatrics, Karolinska Institute, Novum, 141 86, Huddinge, Sweden.
authors.forename: Ezra
authors.initials: E
authors.lastname: Mulugeta
authors.forename: Evert
authors.initials: E
authors.lastname: Karlsson
authors.forename: Atiqul
authors.initials: A
authors.lastname: Islam
authors.forename: Raj
authors.initials: R
authors.lastname: Kalaria
authors.forename: Halinder
authors.initials: H
authors.lastname: Mangat
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Abdu
authors.initials: A
authors.lastname: Adem
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism; D004546:Elapid Venoms; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D010276:Parasympatholytics; D010890:Pirenzepine / Q000031:analogs & derivatives*; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000378:metabolism*
chemical_list: D004546:Elapid Venoms; D010276:Parasympatholytics; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; C098184:muscarinic toxin MT4; C418967:muscarinic toxin-like protein 1; C034915:toxin I, black mamba venom; C065959:AFDX 384; D010890:Pirenzepine