Capsaicinoids Regulate Airway Anion Transporters through Rho Kinase– and Cyclic AMP–Dependent Mechanisms

To investigate the effects of capsaicinoids on airway anion transporters, we recorded and analyzed transepithelial currents in human airway epithelial Calu-3 cells. Application of capsaicin (100 μM) attenuated vectorial anion transport, estimated as short-circuit currents (ISC), before and after stimulation by forskolin (10 μM) with concomitant reduction of cytosolic cyclic AMP (cAMP) levels. The capsaicin-induced inhibition of ISC was also observed in the response to 8-bromo-cAMP (1 mM, a cell-permeable cAMP analog) and 3-isobutyl-1-methylxanthine (1 mM, an inhibitor of phosphodiesterases). The capsaicin-induced inhibition of ISC was attributed to suppression of bumetanide (an inhibitor of the basolateral Na+-K+-2 Cl− cotransporter 1)- and 4,4′-dinitrostilbene-2,2′-disulfonic acid (an inhibitor of basolateral HCO3−-dependent anion transporters)–sensitive components, which reflect anion uptake via basolateral cAMP-dependent anion transporters. In contrast, capsaicin potentiated apical Cl− conductance, whi...