Linoleic Acid Derivative DCP-LA Stimulates Vesicular Transport of α7 ACh Receptors Towards Surface Membrane

Background/Aims: We have earlier found that the linoleic acid derivative DCP-LA could ameliorate learning and memory impairment by targeting alpha 7 ACh receptor. The present study aimed at understanding DCP-LA-regulated alpha 7 ACh receptor trafficking. Methods: We monitored currents through alpha 7 ACh receptors expressed in Xenopus oocytes and assayed the receptor mobilizations using fractions with a sucrose density gradient centrifugation, synaptosome preparation, and acutely dissociated neurons from rat hippocampal slices. Results: DCP-LA persistently potentiated alpha 7 ACh receptor currents, and the effect was inhibited by a protein kinase C (PKC) inhibitor or vesicular transport inhibitors. DCP-LA did not induce PKC phosphorylation of alpha 7 ACh receptors. DCP-LA stimulated translocation of alpha 7 ACh receptors from the cytosol toward the plasma membrane or from extra-synaptosomes into synaptosomes and accumulated the receptors at the presynaptic site in hippocampal neurons. Conclusion: The results of the present study demonstrate that DCP-LA increases surface localization of alpha 7 ACh receptors in hippocampal neurons, specifically at presynaptic terminals, by stimulating vesicular transport of the receptors, resulting in potentiation of alpha 7 ACh receptor responses, regardless of PKC phosphorylation of the receptors. Copyright (c) 2012 S. Karger AG, Basel