Fig. 3.

Structure-activity studies with tryptamine derivatives and the rSERT D98E mutant implicate a direct interaction between neurotransmitter and D98. A, Proposed model for interactions between carboxylic acid of SERT D98 and tryptamine alkylamine group. B, Disruption of carboxylic acid–amine interaction by shortening DMT to the methylamine structure gramine. C, Reestablishing carboxylic acid–amine interactions by lengthening carboxylic acid alkyl chain by one methyl group (D98E) combined with shorter methylamine substrate gramine. D, Evaluation of DMT and gramine potency for inhibition of [³H]5HT uptake at wild-type rSERT and D98E mutant. [³H]5HT uptake assays were performed with transiently transfected COS-7 cells as described in Materials and Methods, with increasing concentrations of DMT or gramine added simultaneously with the addition of 10 nm[³H]5HT. Nonspecific uptake was determined in COS-7 cells transfected with the parent vector pcDNA3 and subtracted from total values. Data were plotted as percentage of specific 5HT uptake. All data plotted represent means ± SEM of triplicate determinations and are representative of three separate experiments. Apparent K_i values are presented in Table2.