title: Activation of CFTR chloride current by nitric oxide in human T lymphocytes.
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.
authors.affiliation: Department of Molecular Pharmacology and Medicine, Stanford University School of Medicine, CA 94305, USA.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Dong
authors.forename: A C
authors.initials: AC
authors.lastname: Chao
authors.forename: K
authors.initials: K
authors.lastname: Kouyama
authors.forename: Y P
authors.initials: YP
authors.lastname: Hsu
authors.forename: R C
authors.initials: RC
authors.lastname: Bocian
authors.forename: R B
authors.initials: RB
authors.lastname: Moss
authors.forename: P
authors.initials: P
authors.lastname: Gardner
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology*; D002999:Clone Cells; D006152:Cyclic GMP / Q000502:physiology; D003550:Cystic Fibrosis / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000634:Aminoquinolines; C505032:CFTR protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP