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Cholesterol reduction attenuates 5-HT1A receptor-mediated signaling in human primary neuronal cultures

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Abstract

Lipid rafts regulate functions of various G protein-coupled receptors and signaling proteins. We show that human primary neuronal cultures contain high levels of 5-HT1A receptors. Stimulation with the 5-HT1A/7 receptor agonist, 8-OH-DPAT, reduced P-T185/Y187-ERK2. This reduction could be blocked by the 5-HT1A receptor antagonist, WAY100635. Pretreatment with the cholesterol sequestering agent, methyl-β-cyclodextrin, before adding 8-OH-DPAT, significantly counteracted the inhibitory influence of 8-OH-DPAT on P-T185/Y187-ERK2 and P-S133-CREB. These data indicate that reduction of cholesterol levels significantly influence signaling via 5-HT1A receptors in intact neurons.

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Acknowledgements

This article is dedicated to Professor Gabriel Fried who passed away during these studies. This study was financially supported by Vetenskapsrådet, Hjärnfonden, Torsten och Ragnar Söderbergs stiftelse.

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There is no conflict of interest.

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Authors and Affiliations

  1. Section for Translational Neuropharmacology, Department of Physiology and Pharmacology, Karolinska Institute, Nanna Svartz väg 2, 171 77, Stockholm, Sweden

    Benita Sjögren & Per Svenningsson

  2. Division of Obstetrics and Gynecology, Department of Women and Child Health, Karolinska Institute, 171 76, Stockholm, Sweden

    Linda Csöregh

Authors
  1. Benita Sjögren
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  2. Linda Csöregh
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  3. Per Svenningsson
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Correspondence to Per Svenningsson.

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Sjögren, B., Csöregh, L. & Svenningsson, P. Cholesterol reduction attenuates 5-HT1A receptor-mediated signaling in human primary neuronal cultures. Naunyn-Schmied Arch Pharmacol 378, 441–446 (2008). https://doi.org/10.1007/s00210-008-0323-6

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  • DOI: https://doi.org/10.1007/s00210-008-0323-6

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