Diphenyleneiodonium, an inhibitor of NOXes and DUOXes, is also an iodide-specific transporter

•Diphenyleneiodonium (DPI) inhibits H2O2 generation by thyroid DUOXes in the μM range.•DPI activates iodide efflux from thyroid, thyroid-derived and unrelated cells in the μM range.•DPI does not activate the efflux of the iodide analog99mTcO4− or of 86Rb+ in the same cells.•DPI thus behaves as a specific ionophore for iodide.

NADPH oxidases (NOXes) and dual oxidases (DUOXes) generate O2.− and H2O2. Diphenyleneiodonium (DPI) inhibits the activity of these enzymes and is often used as a specific inhibitor. It is shown here that DPI, at concentrations similar to those which inhibit the generation of O2 derivatives, activated the efflux of radioiodide but not of its analog 99mTcO4− nor of the K+ cation mimic 86Rb+ in thyroid cells, in the PCCl3 rat thyroid cell line and in COS cell lines expressing the iodide transporter NIS. Effects obtained with DPI, especially in thyroid cells, should therefore be interpreted with caution.