Several phosphate transport processes are present in vascular smooth muscle cells.

We have studied inorganic phosphate (P) handling in rat aortic vascular smooth muscle cells (VSMC) using P-radiotracer assays. Our results have revealed a complex set of mechanisms consisting of ) well-known PiT1/PiT2-mediated sodium-dependent P transport; ) Slc20-unrelated sodium-dependent P transport that is sensitive to the stilbene derivatives 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 4-acetamido-4-isothiocyanostilbene-2,2-disulfonate (SITS); ) a sodium-independent P uptake system that is competitively inhibited by sulfate, bicarbonate, and arsenate and is weakly inhibited by DIDS, SITS, and phosphonoformate; and ) an exit pathway from the cell that is partially chloride dependent and unrelated to the known anion-exchangers expressed in VSMC. The inhibitions of sodium-independent P transport by sulfate and of sodium-dependent transport by SITS were studied in greater detail. The maximal inhibition by sulfate was similar to that of P itself, with a very high inhibition constant (212 mM). SITS only partially inhibited sodium-dependent P transport, but the was very low (14 µM). Nevertheless, SITS and DIDS did not inhibit P transport in oocytes expressing PiT1 or PiT2. Both the sodium-dependent and sodium-independent transport systems were highly dependent on VSMC confluence and on the differentiation state, but they were not modified by incubating VSMC for 7 days with 2 mM P under nonprecipitating conditions. This work not only shows that the P handling by cells is highly complex but also that the transport systems are shared with other ions such as bicarbonate or sulfate. In addition to the inorganic phosphate (P) transporters PiT1 and PiT2, rat vascular smooth muscle cells show a sodium-dependent P transport system that is inhibited by DIDS and SITS. A sodium-independent P uptake system of high affinity is also expressed, which is inhibited by sulfate, bicarbonate, and arsenate. The exit of excess P is through an exchange with extracellular chloride. Whereas the metabolic effects of the inhibitors, if any, cannot be discarded, kinetic analysis during initial velocity suggests competitive inhibition.