Choroid plexus (CP) inorganic phosphate (Pi) transport: Stress‐induced alteration of PiT‐1 (Slc20A1) localization

Abstract

The CP actively transports Pi from CSF to blood utilizing PiT‐2 (Slc20A2) Na‐dependent transporter. In rats, PiT‐2 is normally located in or near the CP microvilli, positioned for removal of Pi from CSF. PiT‐1 predominates in the vascular endothelium, but a faint, diffuse signal is seen in the CP cell cytosol. In human CP, PiT‐2 is localized as above; however, PiT‐1 predominates in the cytosol of CP epithelial cells with a very faint signal in the vascular endothelium. We hypothesized that the PiT‐1 location may be influenced by pre‐fixation cellular stress. Our objective was to examine the distribution of PiT‐1 in rat lateral CP before and after induction of the cellular stress response. Immunohistochemical localization of PiT‐1 followed three treatments: 1. Fixation immediately after sacrifice; 2. Fixation of explants after 7.5 h in DME/F12 at 37°C and 5%CO2 ; 3. Fixation of explants exposed to 100 μM ZnCl2 in DME/F12 for 6 h followed by Zn‐free medium for 1.5 h. After 7.5 h in control culture medium, PiT‐1 increased markedly in the CP epithelium and was membrane associated. Though fainter than non‐cultured CP, staining was present in the capillary endothelial cells. Following Zn‐induced stress, PiT‐1 was again predominately in the CP epithelial cell membranes, including the microvilli but was absent from the capillary endothelium. We conclude that Pi transport capacity of CP may change with cellular stress. Support by NSF.