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Alzheimer amyloid β/A4 peptide binding sites and a possible 'APP-secretase' activity associated with rat brain cortical membranes

Allsop, D and Yamamoto, T and Kametani, F and Miyazaki, N and Ishii, T (1991) Alzheimer amyloid β/A4 peptide binding sites and a possible 'APP-secretase' activity associated with rat brain cortical membranes. Brain Research, 551 (1-2). pp. 1-9. ISSN 0006-8993

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Abstract

We carried out ligand binding experiments on membranes from rat brain cortical grey matter using radioiodinated beta/A4 8-17, with non-specific binding determined by the addition of 10 microM unlabelled peptide. Specific, reversible binding amounted to 60-75% of total binding and showed a clear dependence on time, temperature, pH and membrane concentration. Kinetic analyses indicated a high-affinity binding site with an apparent KD of 440 pM. However, the ligand was partly degraded with loss of the Ser8, Lys16 and Leu17 residues. Excision of the two C-terminal amino acids was inhibited by EDTA, EGTA, dithiothreitol or Zn2+ but was stimulated by Ca2+ or Mn2+. These studies demonstrate high-affinity binding sites for beta/A4 8-17 (or its derivatives) in rat brain, suggesting that this region may contain a physiologically important amino acid sequence and identify a potential membrane-associated amyloid precursor protein (APP) secretase activity.

Item Type: Article
Journal or Publication Title: Brain Research
Uncontrolled Keywords: Alzheimer Disease ; Amyloid beta-Peptides ; Animals ; Binding Sites ; Cerebral Cortex ; Chromatography, High Pressure Liquid ; Drug Stability ; Ligands ; Male ; Membranes ; Peptides ; Rats ; Rats, Inbred Strains
Subjects: UNSPECIFIED
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 50846
Deposited By: ep_importer_pure
Deposited On: 08 Nov 2011 09:48
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 19:43
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/50846

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