Rapid ReportInhibition of nicotinic acetylcholine receptors by apolipoprotein E-derived peptides in rat hippocampal slices
Section snippets
Peptide synthesis
ApoE-derived peptides were synthesized by Sigma-Genosys (The Woodlands, TX, USA) at a purity of 95% and reconstituted in sterile, deionized water yielding stock concentrations of 15–20 mM. Stock solutions were stored at −20 °C and diluted to desired concentrations on the day of the experiment. The peptides used in this study were acetylated at the amino terminus and amide-capped at the carboxyl terminus, except for ApoE133–140, which contained a free amino terminus. Pentalysine was purchased
Results
Synthetic peptides derived from the low-density lipoprotein receptor (LDLR) binding domain of ApoE have been shown to mimic actions of the holoprotein and serve as useful tools in exploring novel mechanisms of ApoE action (Marques and Crutcher, 2003). Accordingly, a 17 amino acid peptide containing residues 133–149 of ApoE (Ac-LRVRLASHLRKLRKRLL-NH2) was tested for the ability to modulate nAChR-mediated responses in rat hippocampal CA1 stratum radiatum interneurons from acutely isolated slices.
Discussion
The present study demonstrates that a peptide derived from the LDLR binding domain of ApoE inhibits α7-containing nAChRs in hippocampal slices at submicromolar concentrations, and that this activity is maintained within an eight residue fragment (ApoE141–148). While studies have shown that ApoE-derived peptides possess a number of biological functions ranging from neuroprotection (Aono et al., 2003) to neurotoxicity (Tolar et al., 1997), this represents the first electrophysiological study
Acknowledgements
We would like to thank S. Dudek and D. Armstrong for advice in preparing the manuscript.
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