EFFECTS OF BRADYKININ ON NA+ AND CL- TRANSPORT IN HUMAN NASAL EPITHELIUM

Human nasal epithelium (HNE) is a Na+ absorptive epithelium but establishes a baseline Cl- secretory current in the presence of amiloride (10(-4) M, luminal). We compared the effects of an inflammatory mediator, bradykinin (BK), on ion transport in primary cultures of HNE using double-barreled Cl--selective microelectrodes. In untreated HNE, BK (10(-5) M) transiently increased the equivalent short-circuit current (I(eq)). Maximal I(eq) occurred with hyperpolarization of the transepithelial potential difference (V(t)), which was associated with hyperpolarization and decreased resistance of the basolateral membrane; a subsequent depolarization of V(t) was observed that was associated with depolarization and decreased resistance of the apical membrane. Removal of bath Cl- did not affect the BK-induced I(eq) response. In amiloride-treated HNE, the electrical pattern of the BK-induced response was identical, but the magnitude of the I(eq) was reduced by 54% and the change in I(eq) could be abolished by removal of bath Cl-. Equivalent-circuit analysis of the response in amiloride-treated tissues indicated activation of a hyperpolarizing conductance in the basolateral membrane, followed 20-30 s later by activation of an apical Cl- conductance. We conclude that BK stimulates both Na+ absorption in untreated HNE and Cl-secretion in amiloride-treated HNE by activating a basolateral (K+) conductance. Analysis of the entire I(eq) response under both conditions also suggested that BK induces a delayed activation of apical membrane Na+ and Cl- conductances.