Caveolin‐1 affects serotonin binding and cell surface levels of human 5‐HT 7(a) receptors

Studies using HeLa cells expressing 5‐HT 7 receptors showed that detergent resistant membranous lipid rafts purified by sucrose gradient centrifugation contained 5‐HT 7 receptors and caveolin‐1. Caveolin‐1 siRNA‐mediated knockdown or serotonin (5‐HT) treatment caused significant reductions of maximum [ 3 H]5‐HT binding to 5‐HT 7 receptors and total immunoreactivity of membranous 5‐HT 7 receptors in intact cells. Co‐treatment with 5‐HT, caveolin‐1 siRNA and methyl‐β‐cyclodextrin had no additive effects on reducing maximum binding of [ 3 H]5‐HT to 5‐HT 7 receptors. 5‐HT‐mediated reduction of [ 3 H]5‐HT binding to 5‐HT 7 receptors was counteracted by genistein, but not by sucrose. Caveolin‐1, specifically localized in cholesterol‐enriched lipid rafts, appears to regulate constitutive and agonist‐stimulated cell surface levels of 5‐HT 7 receptors via a clathrin‐independent mechanism.