title: UTP regulation of ion transport in alveolar epithelial cells involves distinct mechanisms.
abstract: 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) (DeltaIsc) in both types of cells. Amiloride, an inhibitor of epithelial Na(+) channels (ENaC), abolished the UTP-induced DeltaI(sc) in AEC I, but not in AEC II. The general blocker of K(+) channels, BaCl(2), eliminated the UTP-induced DeltaI(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.
authors: Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA.
authors: Chuanxiu
authors: C
authors: Yang
authors: Lijing
authors: L
authors: Su
authors: Yang
authors: Y
authors: Wang
authors: Lin
authors: L
authors: Liu
mesh_terms: D000042:Absorption / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D015221:Potassium Channels / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2; D015398:Signal Transduction / Q000187:drug effects; D013726:Terbutaline / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology*
chemical_list: D018118:Chloride Channels; D053503:Epithelial Sodium Channels; D026901:Membrane Transport Proteins; D015221:Potassium Channels; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D053773:Transforming Growth Factor beta1; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D003907:Dexamethasone; D013726:Terbutaline; D014544:Uridine Triphosphate