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-T¹⁸⁵/Y¹⁸⁷-ERK2. This reduction could be blocked by the 5-HT_1A 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-HT_1A receptors in intact neurons. [ABSTRACT FROM AUTHOR]