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. Author manuscript; available in PMC: 2022 Jan 1.
Published in final edited form as: Biochem Pharmacol. 2020 Nov 25;183:114349. doi: 10.1016/j.bcp.2020.114349

Figure 3-. Simvastatin decreases the Michaelis-Menten Km for 5-HT uptake without changing Vmax or membrane SERT, and decreases the Ki of fluoxetine.

Figure 3-

A) SERTMyc cells treated with 0.5μM simvastatin for 24hr significantly decreases the Michaelis-Menten Km, but does not change SERT uptake Vmax (n=5/grp, *p<0.0001 t-test comparing vehicle vs. simvastatin Km and Vmax). B) SERTMyc cells treated with 0.5μM simvastatin for 24hr shifts SERT Ki at 100nM 5-HT, with increasing concentrations of SERT inhibitor fluoxetine (n=4/grp, *p<0.05 t-test comparing vehicle vs. simvastatin Ki). C) Simvastatin does not change densitometry measures of SERT in total, membrane separated, and intracellular fractions after 0.5μM, 24hr simvastatin treatment. Representative blots demonstrate enrichment of membrane localized pan-cadherin in membrane and total fractions that is not present in the intracellular fraction, and intracellular fractions with lamin B1. D) Mean values and SEM for SERT uptake Km and Vmax (from graph A) and IC50 and Ki (from graph B) in vehicle and simvastatin-treated cells. Data are represented as mean ± SEM. T=Total SERT, M and Mem=Membrane SERT, I and Intra=Intracellular SERT, V=Vehicle, S=Simvastatin.