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

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2001 Nov 15

PMID 11707576

Citations 88

Authors

P Huang

E R Lazarowski

R Tarran

S L Milgram

R C Boucher

M J Stutts

Affiliations

Soon will be listed here.

Abstract

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 A(2B) adenosine 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.

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