Fig. 2. Effects of phosphate concentration gradient and tenapanor on phosphate absorption in human duodenum monolayer cultures.
(A) Correlation between phosphate flux and initial apical phosphate concentration in human duodenum monolayer cultures from two separate donors (1, 2) after overnight incubation. The reproducibility of phosphate absorption was assessed in experiments from two separate passages for one donor (n = 4 per group). (B) Basolateral phosphate concentration, phosphate flux, and (D) transepithelial electrical resistance (TEER) at different apical phosphate concentrations (1 to 30 mM) in human duodenum monolayer cultures after 4 hours of treatment with tenapanor (1 μM) or vehicle (DMSO) with an initial starting basolateral phosphate concentration of 0 mM (n = 4 to 16 per group). (E) Apical phosphate retention, (F) apical phosphate concentration, (G) basolateral phosphate concentration, and (H) apical fluid volume at different initial apical phosphate concentrations (1 to 30 mM) in human duodenum monolayer cultures after overnight treatment with tenapanor (1 μM) or vehicle (DMSO) with an initial starting basolateral phosphate concentration of 1 mM; data from the donor used to test reproducibility in (A). (I) Effect of tenapanor (1 μM) or vehicle (DMSO) on bidirectional phosphate flux at varying phosphate concentration gradients (1 to 10 mM) in human duodenum monolayer cultures (n = 4 per group). Means ± SEM. *P < 0.05, ***P < 0.001, ****P < 0.0001 versus vehicle; two-way ANOVA, with post hoc testing at each concentration with Bonferroni’s correction (B to I).