(A and B) SERT expression levels are conserved regardless of the Itgb3 genotype. (A) Western blot of native SERT from platelet lysates from Itgb3^+/+, Itgb3^+/–, and Itgb3^–/– mice. (B) Platelets were isolated from Itgb3^+/+, Itgb3^+/–, and Itgb3^–/– mice and incubated with [³H]citalopram (20 nM) for 20 minutes at 4°C. (C) Integrin αIIbβ3 loss of function dramatically reduces SERT uptake activity. Platelets were isolated from Itgb3^+/+, Itgb3^+/–, and Itgb3^–/– mice and [³H]5-HT (50 nM) transport assayed. For B and C, data are shown as mean ± SEM. One-way ANOVA with Dunnett’s post-test, *P < 0.05, n = 5 per group. (D) Immobilized fibrinogen, but not collagen, enhances human platelet SERT uptake activity. Human platelets were seeded on plates coated with either poly-d-lysine, collagen, or fibrinogen and [³H]5-HT uptake measured. One-way ANOVA with Bonferroni’s post-test, *P < 0.05. (E) The competing peptide GRGDSP (1 mM) reverses the fibrinogen-mediated enhancement of SERT activity in seeded human platelets. n = 4. (F) The fibrinogen-mediated enhancement of SERT uptake activity can be partially reversed by the p38 MAPK inhibitor SB203580. Platelets attached to fibrinogen-coated plates were incubated for 10 minutes with fostriecin (1 nM), SB203580 (20 μM), PD98059 (10 μM), H8 (0.1 μM), or genistein (20 μM) before measurement of [³H]5-HT uptake. n = 8. The data for D–F are presented as mean ± SEM with 1-way ANOVA and Dunnett’s post-test, *P < 0.05 and **P < 0.005.