Figure 4.

SERT is refractory to regulation through PKG and p38 MAP kinase signaling pathways. A, SERT Ala56 lacks sensitivity to 8BrcGMP. Homozygous Ala56 cells (10⁶/tube) were preincubated for various lengths of time at 37°C, with 10 μM 8BrcGMP prior to [³H]5-HT transport assays. B, SERT Ala56 lacks sensitivity to the p38 MAPK activator anisomycin; 8BrcGMP effects on Gly56 SERT are completely blocked by coincubation with the PKG inhibitor H8 (10 μM), whereas the p38 MAPK inhibitor SB203580 (1 μM) prevented anisomycin stimulation (data not shown). Data plotted represent mean data ± SD (n=3) for a single cell line of each genotype assayed in parallel. Findings were replicated with identical results in an additional line for each genotype.