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

Naunyn Schmiedebergs Arch Pharmacol. 2008 Oct;378(4):441-6. doi: 10.1007/s00210-008-0323-6. Epub 2008 Jul 8.

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-HT(1A) receptors. Stimulation with the 5-HT(1A/7) receptor agonist, 8-OH-DPAT, reduced P-T(185)/Y(187)-ERK2. This reduction could be blocked by the 5-HT(1A) receptor antagonist, WAY100635. Pretreatment with the cholesterol sequestering agent, methyl-beta-cyclodextrin, before adding 8-OH-DPAT, significantly counteracted the inhibitory influence of 8-OH-DPAT on P-T(185)/Y(187)-ERK2 and P-S(133)-CREB. These data indicate that reduction of cholesterol levels significantly influence signaling via 5-HT(1A) receptors in intact neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • CREB-Binding Protein / metabolism
  • Cells, Cultured
  • Cholesterol / metabolism*
  • Dose-Response Relationship, Drug
  • Ether-A-Go-Go Potassium Channels / metabolism
  • Humans
  • Immunoblotting
  • Intracellular Fluid / drug effects
  • Intracellular Fluid / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phosphorylation / drug effects
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptors, Serotonin / metabolism
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • beta-Cyclodextrins / pharmacology

Substances

  • Ether-A-Go-Go Potassium Channels
  • KCNH6 protein, human
  • Piperazines
  • Pyridines
  • Receptors, Serotonin
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • beta-Cyclodextrins
  • methyl-beta-cyclodextrin
  • serotonin 7 receptor
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Cholesterol
  • CREB-Binding Protein