Cholesterol reduction attenuates 5-HT1A receptor-mediated signaling in human primary neuronal cultures.
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.
Sjögren
Benita
B
Section for Translational Neuropharmacology, Department of Physiology and Pharmacology, Karolinska Institute, Nanna Svartz väg 2, 171 77, Stockholm, Sweden.
Csöregh
Linda
L
Svenningsson
Per
P
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D047392:beta-Cyclodextrins / Q000494:pharmacology
D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002784:Cholesterol; D050882:CREB-Binding Protein