A peptide derived from the C-terminal region of acetylcholinesterase modulates extracellular concentrations of acetylcholinesterase in the rat substantia nigra.
It is well established that acetylcholinesterase (AChE) has 'non-classical' functions independent of cholinergic transmission. A region of AChE distinct from the catalytic site may be responsible for these actions via a 14-residue peptide located between residues 586-599 at the C-terminus of human AChE. This AChE-peptide possesses a high amino acid sequence homology with a region of amyloid precursor protein and shares many biophysical and physiological characteristics. In this study, the effect of AChE-peptide (AEFHRWSSYMVHWK) on the extracellular levels of endogenous AChE was examined in rat substantia nigra in vitro. A chemiluminescent assay was used to continuously measure the soluble AChE concentration from tissue punches of the substantia nigra. Application of NMDA evoked an increase in extracellular AChE levels consistent with previous results obtained from in vivo models. AChE-peptide, when applied alone, had no effect on AChE release: however, when co-applied with NMDA, AChE-peptide reduced the effectiveness of NMDA to evoke release of AChE. These results indicate, in a region of the brain central to the aetiology of Parkinson's disease, that an AChE-peptide fragment derived from AChE displays a bioactivity that could involve regulation of Ca(2+) availability and hence the release of AChE.
Emmett
Stevan R
SR
University Department of Pharmacology, University of Oxford, Oxford OX1 3QY, UK. steve.emmett@pharm.ox.ac.uk
Greenfield
Susan A
SA
D000109:Acetylcholine / Q000096:biosynthesis*; D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism*; D000595:Amino Acid Sequence / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000502:physiology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010300:Parkinson Disease / Q000201:enzymology / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D016202:N-Methylaspartate; D000110:Acetylcholinesterase; D000109:Acetylcholine