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Amyloid Peptide Aβ 1‐42 Binds Selectively and with Picomolar Affinity to α7 Nicotinic Acetylcholine Receptors
Author(s) -
Wang HoauYan,
Lee Daniel H. S.,
Davis Coralie B.,
Shank Richard P.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0751155.x
Subject(s) - acetylcholine receptor , nicotinic agonist , peptide , chemistry , receptor , ganglion type nicotinic receptor , acetylcholine , alpha 4 beta 2 nicotinic receptor , amyloid (mycology) , biochemistry , neuroscience , biophysics , nicotinic acetylcholine receptor , microbiology and biotechnology , pharmacology , biology , inorganic chemistry
We have recently reported evidence that a very high affinity interaction between the β‐amyloid peptide Aβ 1‐42 and the α7 nicotinic acetylcholine receptor (α7nAChR) may be a precipitating event in the formation of amyloid plaques in Alzheimer's disease. In the present study, the kinetics for the binding of Aβ 1‐42 to α7nAChR and α4β2nAChR were determined using the subtype‐selective nicotinic receptor ligands [ 3 H]methyllycaconitine and [ 3 H]cytisine. Synaptic membranes prepared from rat and guinea pig cerebral cortex and hippocampus were used as the source of receptors. Aβ 1‐42 bound to the α7nAChR with exceptionally high affinity, as indicated by K i values of 4.1 and 5.0 p M for rat and guinea pig receptors, respectively. When compared with the α7nAChR, the affinity of Aβ 1‐42 for the α4β2nAChR was ∼5,000‐fold lower, as indicated by corresponding K i values of 30 and 23n M . The results of this study support the concept that an exceptionally high affinity interaction between Aβ 1‐42 and α7nAChR could serve as a precipitating factor in the formation of amyloid plaques and thereby contribute to the selective degeneration of cholinergic neurons that originate in the basal forebrain and project to the cortex and hippocampus.