Human SLC26A4 Stable Cell Line - HEK293

Pendrin (solute carrier family 26, member A4; SLC26A4) is an electroneutrally active, Na+-independent Cl-/I-/HCO3- exchanger whose dysfunction results in neurological autosomal recessive syndrome (Pendred syndrome) or nonsyndromic deafness (DFNB4) with and without thyroid involvement, respectively. In addition to being expressed in the inner ear and thyroid, pendrin is also found in the kidney and airways. As pendrin inhibition may represent a novel strategy for treating a variety of disease states, considerable effort has been devoted to the identification of pendrin blockers.

A review of the literature on the ability of several compounds (i.e., several known ion transport inhibitors) to block pendrin activity revealed inconsistent results. These inconsistent findings may be due in part to the concentration of the compounds and/or the nature of the model systems used in the studies. Here the researchers present a functional screen of 22 small molecules on pendrin-driven iodide influx at relatively low concentrations (0.1 mM) after overexpression of human pendrin (SLC26A4) in a human kidney cell line, with the goal of (i) elucidating previously conflicting results and (ii) confirming findings previously obtained using different techniques and/or model cell systems. The results of this study demonstrate that clinically effective nonsteroidal anti-inflammatory drugs (niflumic acid and tenidap) directly inhibit pendrin activity.

Figure 1. Pendrin activity is sensitive to niflumic acid and tenidap. Representative raw recordings of intracellular fluorescence intensity (left) and percent fluorescence decrease (ΔF%, right) were measured in HEK 293 Phoenix cells transfected with pendrin (SLC26A4, white bars) or control cells (control, black bars) in the presence of 0.1 mM (a) niflumic acid (NFA; n = 12) or (b) tenidap (n = 48) or the corresponding vehicle. (Bernardinelli E, et al., 2016)