Abstract
Nitric oxide, which is produced by cytokine-activated mononuclear cells, is thought to play an important role in inflammation and immunity. While the function of nitric oxide as a direct cytotoxic effector molecule is well established, its function as a transducer molecule in immune cells is not. By use of whole-cell patch clamp recordings, we show that nitric oxide activates cystic fibrosis transmembrane conductance regulator CI- currents in normal human cloned T cells by a cGMP-dependent mechanism. This pathway is defective in cystic fibrosis-derived human cloned T cells. These findings not only delineate a novel transduction mechanism for nitric oxide but also support the hypothesis that an intrinsic immune defect may exist in cystic fibrosis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aminoquinolines / pharmacology
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Arginine / pharmacology
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CD4-Positive T-Lymphocytes / physiology*
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Chloride Channels / physiology*
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Clone Cells
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Cyclic GMP / physiology
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Cystic Fibrosis / physiopathology
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Cystic Fibrosis Transmembrane Conductance Regulator
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Guanylate Cyclase / antagonists & inhibitors
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Humans
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Membrane Proteins / physiology*
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Nitric Oxide / pharmacology
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Nitric Oxide / physiology*
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Patch-Clamp Techniques
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Penicillamine / analogs & derivatives
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Penicillamine / pharmacology
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S-Nitroso-N-Acetylpenicillamine
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Signal Transduction / drug effects
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Signal Transduction / physiology*
Substances
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Aminoquinolines
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CFTR protein, human
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Chloride Channels
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Membrane Proteins
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Cystic Fibrosis Transmembrane Conductance Regulator
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Nitric Oxide
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S-Nitroso-N-Acetylpenicillamine
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6-anilino-5,8-quinolinedione
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Arginine
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Guanylate Cyclase
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Penicillamine
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Cyclic GMP