UTP regulation of ion transport in alveolar epithelial cells involves distinct mechanisms

UTP is known to regulate alveolar fluid clearance. However, the relative contribution of alveolar type I cells and type II cells to this process is unknown. In this study, we investigated the effects of UTP on ion transport in type I-like cell (AEC I) and type II-like cell (AEC II) monolayers. Luminal treatment of cell monolayers with UTP increased short-circuit current (I _sc) of AEC II but decreased I_sc of AEC I. The Cl ^- channel blockers NPPB and DIDS inhibited the UTP-induced changes in I_sc (ΔIsc) in both types of cells. Amiloride, an inhibitor of epithelial Na⁺ channels (ENaC), abolished the UTP-induced ΔI_sc in AEC I, but not in AEC II. The general blocker of K ⁺ channels, BaCl₂, eliminated the UTP-induced ΔI_sc in AEC II, but not in AEC I. The intermediate conductance (IK_Ca) blocker, clofilium, also blocked the UTP effect in AEC II. The signal transduction pathways mediated by UTP were the same in AEC I and AEC II. Furthermore, UTP increased Cl^- secretion in AEC II and Cl ^- absorption in AEC I. Our results suggest that UTP induces opposite changes in I_sc in AEC I and AEC II, likely due to the reversed Cl^- flux and different contributions of ENaC and IK_Ca. Our results further imply a new concept that type II cells contribute to UTP-induced fluid secretion and type I cells contribute to UTP-induced fluid absorption in alveoli.