Bioactivity of a peptide derived from acetylcholinesterase: electrophysiological characterization in guinea-pig hippocampus.
Acetylcholinesterase is well known to have noncholinergic functions. Only recently, however, has the salient part been identified of the molecule responsible for these nonclassical actions, a peptide of 14 amino acids towards the C-terminus of acetylcholinesterase. The aim of this study was to test the bioactivity of this 'acetylcholinesterase-peptide' using intracellular recordings in guinea-pig hippocampal slices. In the presence of tetrodotoxin, acetylcholinesterase-peptide alone affected neither the membrane potential nor the input resistance of CA1 neurons; however, a modulatory action was observed, as a concentration-dependent decrease of N-methyl-d-aspartic acid-induced depolarization. When calcium potentials were elicited by a depolarizing current pulse, application of acetylcholinesterase-peptide increased or reduced the degree of calcium spike firing in, respectively, the presence or absence of the N-methyl-d-aspartic acid antagonist d(-)-2-amino-5-phosphonopentanoic acid. In contrast, a peptide derived from the equivalent region of butyrylcholinesterase, which also hydrolyses acetylcholine, had no effect. In conclusion, acetylcholinesterase-peptide has a selective bioactivity in the hippocampus; it could thus offer new ways of targeting mechanisms of calcium-induced neurotoxicity.
Bon
Christelle L M
CL
University Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK. c.bon@ucl.ac.uk
Greenfield
Susan A
SA
D000110:Acetylcholinesterase / Q000494:pharmacology* / Q000502:physiology; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004594:Electrophysiology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D010446:Peptide Fragments / Q000302:isolation & purification / Q000494:pharmacology* / Q000502:physiology
D010446:Peptide Fragments; D016202:N-Methylaspartate; D000110:Acetylcholinesterase