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Molecular Pharmacology

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Research ArticleArticle

ORKAMBI-Mediated Rescue of Mucociliary Clearance in Cystic Fibrosis Primary Respiratory Cultures Is Enhanced by Arginine Uptake, Arginase Inhibition, and Promotion of Nitric Oxide Signaling to the Cystic Fibrosis Transmembrane Conductance Regulator Channel

Yu-Sheng Wu, Janet Jiang, Saumel Ahmadi, Alexandria Lew, Onofrio Laselva, Sunny Xia, Claire Bartlett, Wan Ip, Leigh Wellhauser, Hong Ouyang, Tanja Gonska, Theo J. Moraes and Christine E. Bear
Molecular Pharmacology October 2019, 96 (4) 515-525; DOI: https://doi.org/10.1124/mol.119.117143
Yu-Sheng Wu
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Janet Jiang
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Saumel Ahmadi
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Alexandria Lew
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Onofrio Laselva
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Sunny Xia
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Claire Bartlett
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Wan Ip
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Leigh Wellhauser
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Hong Ouyang
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Tanja Gonska
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Theo J. Moraes
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Christine E. Bear
Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
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Article Information

vol. 96 no. 4 515-525
DOI 
https://doi.org/10.1124/mol.119.117143
PubMed 
31427400

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0026-895X
Online ISSN 
1521-0111
History 
  • Received May 7, 2019
  • Accepted August 1, 2019
  • Published online September 17, 2019.

Article Versions

  • Earlier version (August 19, 2019 - 11:57).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics

Author Information

  1. Yu-Sheng Wu,
  2. Janet Jiang,
  3. Saumel Ahmadi,
  4. Alexandria Lew,
  5. Onofrio Laselva,
  6. Sunny Xia,
  7. Claire Bartlett,
  8. Wan Ip,
  9. Leigh Wellhauser,
  10. Hong Ouyang,
  11. Tanja Gonska,
  12. Theo J. Moraes, and
  13. Christine E. Bear
  1. Programmes in Translational Medicine (Y.-S.W., C.B., W.I., H.O., T.G., T.J.M.) and Molecular Medicine (Y.-S.W., J.J., S.A., A.L., O.L., S.X., L.W., C.E.B.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; and Departments of Laboratory Medicine and Pathobiology (T.J.M.), Biochemistry (C.E.B.), Physiology (Y.-S.W., S.A., O.L., S.X., C.E.B.), and Paediatrics (T.G., T.J.M.), University of Toronto, Toronto, Ontario, Canada
  1. Address correspondence to:
    Dr. Christine E. Bear, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, 686 Bay Street, Toronto, Canada. E-mail: bear{at}sickkids.ca
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Molecular Pharmacology: 96 (4)
Molecular Pharmacology
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1 Oct 2019
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ORKAMBI-Mediated Rescue of Mucociliary Clearance in Cystic Fibrosis Primary Respiratory Cultures Is Enhanced by Arginine Uptake, Arginase Inhibition, and Promotion of Nitric Oxide Signaling to the Cystic Fibrosis Transmembrane Conductance Regulator Chann…
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Research ArticleArticle

Nitric Oxide Boosts Rescue of F508del-CFTR by ORKAMBI

Yu-Sheng Wu, Janet Jiang, Saumel Ahmadi, Alexandria Lew, Onofrio Laselva, Sunny Xia, Claire Bartlett, Wan Ip, Leigh Wellhauser, Hong Ouyang, Tanja Gonska, Theo J. Moraes and Christine E. Bear
Molecular Pharmacology October 1, 2019, 96 (4) 515-525; DOI: https://doi.org/10.1124/mol.119.117143

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Research ArticleArticle

Nitric Oxide Boosts Rescue of F508del-CFTR by ORKAMBI

Yu-Sheng Wu, Janet Jiang, Saumel Ahmadi, Alexandria Lew, Onofrio Laselva, Sunny Xia, Claire Bartlett, Wan Ip, Leigh Wellhauser, Hong Ouyang, Tanja Gonska, Theo J. Moraes and Christine E. Bear
Molecular Pharmacology October 1, 2019, 96 (4) 515-525; DOI: https://doi.org/10.1124/mol.119.117143
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