Treatment of transfected HeLa cells with PKGI siRNA prevents 8-Br-cGMP-induced SERT stimulation. Cells were transfected with hSERT and siRNA directed against human PKGI and assayed for 8-Br-cGMP stimulation of SERT activity as described in Methods. Upon 8-Br-cGMP stimulation, cells expressing hSERT (closed bar) demonstrate elevated 5-HT transport activity (147 ± 3.56%) absent from cells treated with PKGI siRNA (dotted bar, 96.4 ± 6.96%). Cells treated with siRNA in the absence of 8-Br-cGMP (checkered bar) show no change in 5-HT uptake (94.5 ± 1.88%) from control (open bar, 100 ± 0.010%). Each assay was repeated three times. Values are means ± SEM. ***, p < 0.001 versus control, calculated via one-way ANOVA followed by Tukey's post-test.