Differential Physiologic Responses of alpha7 Nicotinic Acetylcholine Receptors to beta-amyloid1-40 and beta-amyloid1-42

J Neurobiol. 2003 Apr;55(1):25-30. doi: 10.1002/neu.10203.

Abstract

The beta-amyloid peptides (Abeta), Abeta(1-40) and Abeta(1-42), have been implicated in Alzheimer's disease (AD) pathology. Although Abeta(1-42) is generally considered to be the pathological peptide in AD, both Abeta(1-40) and Abeta(1-42) have been used in a variety of experimental models without discrimination. Here we show that monomeric or oligomeric forms of the two Abeta peptides, when interact with the neuronal cation channel, alpha7 nicotinic acetylcholine receptors (alpha7nAChR), would result in distinct physiologic responses as measured by acetylcholine release and calcium influx experiments. While Abeta(1-42) effectively attenuated these alpha7nAChR-dependent physiology to an extent that was apparently irreversible, Abeta(1-40) showed a lower inhibitory activity that could be restored upon washings with physiologic buffers or treatment with alpha7nAChR antagonists. Our data suggest a clear pharmacological distinction between Abeta(1-40) and Abeta(1-42).

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholine / metabolism
  • Alkaloids / pharmacology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Atropine / pharmacology
  • Azocines
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Conotoxins / pharmacology
  • Dose-Response Relationship, Drug
  • Frontal Lobe / metabolism
  • In Vitro Techniques
  • Muscarinic Antagonists / pharmacology
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Nicotinic Antagonists / pharmacology
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Potassium / pharmacology
  • Pyridines / pharmacology
  • Quinolizines
  • Rats
  • Receptors, Nicotinic / metabolism*
  • Subcellular Fractions
  • Synaptosomes / metabolism

Substances

  • Alkaloids
  • Amyloid beta-Peptides
  • Azocines
  • Bridged Bicyclo Compounds, Heterocyclic
  • Calcium Channel Blockers
  • Conotoxins
  • Muscarinic Antagonists
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Peptide Fragments
  • Pyridines
  • Quinolizines
  • Receptors, Nicotinic
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • cytisine
  • Nicotine
  • Atropine
  • epibatidine
  • Acetylcholine
  • Potassium
  • Calcium