NSAIDs inhibit Kv1.3 expression in IEC‐6 cells and rat duodenum (840.8)

Abstract

Clinical use of non‐steroidal anti‐inflammatory drugs (NSAIDs) is well known to cause gastrointestinal ulcer formation via several mechanisms that include inhibiting epithelial cell migration and mucosal restitution. The drug‐affected signaling pathways that contribute to the toxic side‐effects of NSAIDs are poorly understood. Previous studies have shown that NSAIDs inhibit cell migration in vitro by depolarizing membrane potential and suppressing expression of voltage‐gated potassium channel subunits. Kv1.3, in particular, is known to play an important role in cell migration, and results from a microarray study suggested that its expression is affected by NSAID treatment. Accordingly, we investigated the effects of NSAIDs on Kv1.3 mRNA and protein expression in a rat duodenal cell line (IEC‐6) or the duodenum of whole rats treated with indomethacin or NS‐398 for 72 h. Treatment of IEC‐6 cells with indomethacin or NS‐398 significantly reduced total and plasma membrane protein expression of Kv1.3. In rat duodenum, our results showed that expression of Kv1.3 mRNA was significantly decreased by NS‐398, but not indomethacin, and that Kv1.3 protein expression was significantly decreased following treatment with either NSAID. These results suggest that inhibition of epithelial cell migration by NSAIDs is associated with a decreased expression of Kv1.3 channels.Grant Funding Source: Supported by National Institutes of Diabetes and Digestive and Kidney Diseases (1R15DK091791)