Abstract
Although Cl- transport in fetal lung is important for fluid secretion and normal lung development, the role of Cl- transport in adult lung is not well understood. In physiological studies, the cystic fibrosis transmembrane regulator (CFTR) plays a role in fluid absorption in the distal air spaces of adult lung, and alveolar type II cells cultured for 5 days have the capacity to transport Cl-. Although both alveolar type I and type II cells express CFTR, it has previously not been known whether type I cells transport Cl-. We studied Cl- uptake in isolated type I cells directly, using either radioisotopic tracers or halide-sensitive fluorescent indicators. By both methods, type I cells take up Cl-. In the presence of beta-adrenergic agonist stimulation, Cl- uptake can be inhibited by CFTR antagonists. Type I cells express both the Cl-/HCO3- anion exchanger AE2 and the voltage-gated Cl- channels CLC5 and CLC2. Inhibitors of AE2 also block Cl- uptake in type I cells. Together, these results demonstrate that type I cells are capable of Cl- uptake and suggest that the effects seen in whole lung studies establishing the importance of Cl- movement in alveolar fluid clearance may be, in part, the result of Cl- transport across type I cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
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Adrenergic beta-Agonists / pharmacology
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Amiloride / pharmacology
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Animals
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Anion Transport Proteins / genetics
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Anion Transport Proteins / metabolism
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Antiporters / genetics
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Antiporters / metabolism
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Bumetanide / pharmacology
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Chlorides / metabolism*
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Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism*
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Fluorescence
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Gene Expression Regulation / drug effects
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Immunohistochemistry
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Nitrobenzoates / pharmacology
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Pulmonary Alveoli / cytology*
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Quinolinium Compounds / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Radioisotopes
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Rats
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Rats, Sprague-Dawley
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SLC4A Proteins
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Terbutaline / pharmacology
Substances
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Adrenergic beta-Agonists
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Anion Transport Proteins
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Antiporters
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Chlorides
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Nitrobenzoates
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Quinolinium Compounds
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RNA, Messenger
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Radioisotopes
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SLC4A Proteins
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Bumetanide
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Cystic Fibrosis Transmembrane Conductance Regulator
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N-(ethoxycarbonylmethyl)-6-methoxyquinolinium
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5-nitro-2-(3-phenylpropylamino)benzoic acid
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Amiloride
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Terbutaline
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid