Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia

Airway epithelia are confronted with distinct signals emanating from the luminal and/or serosal environments. This study tested whether airway epithelia exhibit polarized intracellular free calcium (Ca2+ i) and anion secretory responses to 5′ triphosphate nucleotides (ATP/UTP), which may be released...

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Main Authors:	Paradiso, Anthony M., Ribeiro, Carla M.P., Boucher, Richard C.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2001
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2232471/

id	pubmed-2232471
recordtype	oai_dc
spelling	pubmed-22324712008-04-21 Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia Paradiso, Anthony M. Ribeiro, Carla M.P. Boucher, Richard C. Original Article Airway epithelia are confronted with distinct signals emanating from the luminal and/or serosal environments. This study tested whether airway epithelia exhibit polarized intracellular free calcium (Ca2+ i) and anion secretory responses to 5′ triphosphate nucleotides (ATP/UTP), which may be released across both barriers of these epithelia. In both normal and cystic fibrosis (CF) airway epithelia, mucosal exposure to ATP/UTP increased Ca2+ i and anion secretion, but both responses were greater in magnitude for CF epithelia. In CF epithelia, the mucosal nucleotide–induced response was mediated exclusively via Ca2+ i interacting with a Ca2+-activated Cl− channel (CaCC). In normal airway epithelia (but not CF), nucleotides stimulated a component of anion secretion via a chelerythrine-sensitive, Ca2+-independent PKC activation of cystic fibrosis transmembrane conductance regulator. In normal and CF airway epithelia, serosally applied ATP or UTP were equally effective in mobilizing Ca2+ i. However, serosally applied nucleotides failed to induce anion transport in CF epithelia, whereas a PKC-regulated anion secretory response was detected in normal airway epithelia. We conclude that (1) in normal nasal epithelium, apical/basolateral purinergic receptor activation by ATP/UTP regulates separate Ca2+-sensitive and Ca2+-insensitive (PKC-mediated) anion conductances; (2) in CF airway epithelia, the mucosal ATP/UTP-dependent anion secretory response is mediated exclusively via Ca2+ i; and (3) Ca2+ i regulation of the Ca2+-sensitive anion conductance (via CaCC) is compartmentalized in both CF and normal airway epithelia, with basolaterally released Ca2+ i failing to activate CaCC in both epithelia. The Rockefeller University Press 2001-01-01 /pmc/articles/PMC2232471/ /pubmed/11134231 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Paradiso, Anthony M. Ribeiro, Carla M.P. Boucher, Richard C.
spellingShingle	Paradiso, Anthony M. Ribeiro, Carla M.P. Boucher, Richard C. Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia
author_facet	Paradiso, Anthony M. Ribeiro, Carla M.P. Boucher, Richard C.
author_sort	Paradiso, Anthony M.
title	Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia
title_short	Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia
title_full	Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia
title_fullStr	Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia
title_full_unstemmed	Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia
title_sort	polarized signaling via purinoceptors in normal and cystic fibrosis airway epithelia
description	Airway epithelia are confronted with distinct signals emanating from the luminal and/or serosal environments. This study tested whether airway epithelia exhibit polarized intracellular free calcium (Ca2+ i) and anion secretory responses to 5′ triphosphate nucleotides (ATP/UTP), which may be released across both barriers of these epithelia. In both normal and cystic fibrosis (CF) airway epithelia, mucosal exposure to ATP/UTP increased Ca2+ i and anion secretion, but both responses were greater in magnitude for CF epithelia. In CF epithelia, the mucosal nucleotide–induced response was mediated exclusively via Ca2+ i interacting with a Ca2+-activated Cl− channel (CaCC). In normal airway epithelia (but not CF), nucleotides stimulated a component of anion secretion via a chelerythrine-sensitive, Ca2+-independent PKC activation of cystic fibrosis transmembrane conductance regulator. In normal and CF airway epithelia, serosally applied ATP or UTP were equally effective in mobilizing Ca2+ i. However, serosally applied nucleotides failed to induce anion transport in CF epithelia, whereas a PKC-regulated anion secretory response was detected in normal airway epithelia. We conclude that (1) in normal nasal epithelium, apical/basolateral purinergic receptor activation by ATP/UTP regulates separate Ca2+-sensitive and Ca2+-insensitive (PKC-mediated) anion conductances; (2) in CF airway epithelia, the mucosal ATP/UTP-dependent anion secretory response is mediated exclusively via Ca2+ i; and (3) Ca2+ i regulation of the Ca2+-sensitive anion conductance (via CaCC) is compartmentalized in both CF and normal airway epithelia, with basolaterally released Ca2+ i failing to activate CaCC in both epithelia.
publisher	The Rockefeller University Press
publishDate	2001
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2232471/
_version_	1611438222030667776

Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia

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