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Compartmentalized Autocrine Signaling to Cystic Fibrosis Transmembrane Conductance Regulator at the Apical Membrane of Airway Epithelial Cells

Huang, Pingbo ; Lazarowski, Eduardo R. ; Tarran, Robert ; Milgram, Sharon L. ; Boucher, Richard C. ; Stutts, M. Jackson

Proceedings of the National Academy of Sciences - PNAS, 2001-11, Vol.98 (24), p.14120-14125 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Compartmentalized Autocrine Signaling to Cystic Fibrosis Transmembrane Conductance Regulator at the Apical Membrane of Airway Epithelial Cells
Autor: Huang, Pingbo ; Lazarowski, Eduardo R. ; Tarran, Robert ; Milgram, Sharon L. ; Boucher, Richard C. ; Stutts, M. Jackson
Assuntos: Adenosine - antagonists & inhibitors ; Adenosine - metabolism ; Adenosine - pharmacology ; Adenosine Triphosphate - metabolism ; Adenylyl Cyclases - metabolism ; Autocrine Communication - physiology ; Biological Sciences ; Cell Line ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cell Membrane - physiology ; Cell membranes ; Cells ; Chlorides - metabolism ; Cyclic AMP - metabolism ; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors ; Cystic fibrosis ; Cystic Fibrosis - metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism ; Electrophysiology ; Epithelial cells ; Epithelial Cells - cytology ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial Cells - physiology ; GTP-Binding Protein alpha Subunits, Gs - physiology ; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology ; Humans ; Ion channels ; Liquids ; Lung - cytology ; Membranes ; P branes ; Physiological regulation ; Pipettes ; Receptor, Adenosine A2B ; Receptors ; Receptors, Purinergic P1 - metabolism ; Secretion
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2001-11, Vol.98 (24), p.14120-14125
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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To whom reprint requests should be addressed. E-mail: huangp@med.unc.edu.
Edited by Peter C. Agre, Johns Hopkins University School of Medicine, Baltimore, MD, and approved September 18, 2001
Descrição: Physical stimulation of airway surfaces evokes liquid secretion, but the events that mediate this vital protective function are not understood. When cystic fibrosis transmembrane conductance regulator (CFTR) channel activity was used as a functional readout, we found signaling elements compartmentalized at both extracellular and intracellular surfaces of the apical cell membrane that activate apical Cl-conductance in Calu-3 cells. At the outer surface, ATP was released by physical stimuli, locally converted to adenosine, and sensed by A2Badenosine receptors. These receptors couple to G proteins, adenylyl cyclase, and protein kinase A, at the intracellular face of the apical membrane to activate colocalized CFTR. Thus, airways have evolved highly efficient mechanisms to "flush" noxious stimuli from airway surfaces by selective activation of apical membrane signal transduction and effector systems.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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Compartmentalized Autocrine Signaling to Cystic Fibrosis Transmembrane Conductance Regulator at the Apical Membrane of Airway Epithelial Cells

Huang, Pingbo ; Lazarowski, Eduardo R. ; Tarran, Robert ; Milgram, Sharon L. ; Boucher, Richard C. ; Stutts, M. Jackson

United States: National Academy of Sciences

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