Structure-function and pharmacological studies on the mammalian serotonin transporter

Abstract

In Pichia pastoris, the existing membrane ergosterol was replaced by cholesterol in an attempt to improve folding of the low affinity heterologously expressed rat serotonin transporter, as judged by means of radioligand binding of [3H]imipramine. Two methods were used to incorporate cholesterol into the Pichia membranes. Firstly, an in vivo approach was used, which exploited metabolic inhibitors to disrupt the ergosterol biosynthetic pathway and induce a requirement for exogenously supplied cholesterol. Two compounds, lovastatin and pravastatin, were tested for their potency at inhibiting ergosterol production.