Apical versus Basolateral P2Y(6) Receptor-Mediated Cl- Secretion in Immortalized Bronchial Epithelia
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AbstractApical and/or basolateral membranes of polarized epithelia express P2Y receptors, which regulate the transport of fluid and electrolytes. In the airway, P2Y receptors modulate Cl- secretion through the phospholipase C and calcium signaling pathways. Recent evidence suggests that P2Y(6) receptors are expressed in bronchial epithelium and coupled to the cAMP/protein kinase A (PKA) pathways. We examined P2Y receptor subtype expression, including P2Y(6), and the effect of extracellular nucleotides on basal short-circuit current (I-SC) and intracellular calcium concentration ([Ca2+](i)) in a human bronchial epithelial cell line (16HBE14o-). Real-time PCR demonstrated P2Y(1), P2Y(2), P2Y(4), and P2Y(6) receptor expression and confirmed that transcript levels were not altered when cells were grown under varied conditions. It was determined that P2Y agonists (ATP, UTP, UDP) stimulated a concomitant increase in I-SC and [Ca2+](i). Apical nucleotides stimulated an increase in [Ca2+](i) more efficiently than basolateral nucleotides; however, P2Y agonistic effects on I-SC were greater when applied basolaterally. Since the P2Y(6) receptors differentially regulate apical and basolateral UDP-induced I-SC and [Ca2+](i) we investigated membrane-resident P2Y(6) receptor functions using Cl- or K+ channels blockers. Apical and basolateral UDP activation of I-SC was inhibited by applying DIDS apically or TRAM-34 and clotrimazole basolaterally. Although both apical and basolateral UDP increased PKA activity, only apical UDP-induced I-SC was sensitive to a CFTR inhibitor. These data demonstrate that P2Y agonists stimulate Ca2+-dependent Cl- secretion across human bronchial epithelia and that the cAMP/PKA pathway regulates apical but not basolateral P2Y(6) receptor-coupled ion transport in human bronchial epithelia.
All Author(s) ListWong AM, Chow AW, Au SC, Wong CC, Ko WH
Journal nameAmerican Journal of Respiratory Cell and Molecular Biology
Detailed descriptionTo ORKTS: DOI: 10.1165/rcmb.2008-0020OC.
Volume Number40
Issue Number6
PublisherAmerican Thoracic Society
Pages733 - 745
LanguagesEnglish-United Kingdom
Keywordsbronchial epithelium, Ca2+; cAMP; Cl- secretion; P2Y receptors
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Respiratory System; RESPIRATORY SYSTEM

Last updated on 2021-08-03 at 00:03