Activation of VPAC<subscript>1</subscript> receptors by VIP and PACAP-27 in human bronchial epithelial cells induces CFTR-dependent chloride secretion.
In: British Journal of Pharmacology, Jg. 141 (2004-02-15), Heft 4, S. 698-708
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academicJournal
Zugriff:
1: In the human airway epithelium, VIP/PACAP receptors are distributed in nerve fibers and in epithelial cells but their role in transepithelial ion transport have not been reported. Here, we show that human bronchial epithelial Calu-3 cells expressed the VPAC1 receptor subtype which shares similar high affinity for VIP and PACAP-27. 2: The stoichiometric binding parameters characterizing the 125I-VIP and 125I-PACAP-27 binding to these receptors were determined. 3: We found that VIP (EC50˜7.6?nM) and PACAP-27 (EC50˜10?nM) stimulated glibenclamide-sensitive and DIDS-insensitive iodide efflux in Calu-3 cells. 4: The protein kinase A (PKA) inhibitor, H-89 and the protein kinase C (PKC) inhibitor, chelerythrine chloride prevented activation by both peptides demonstrating that PKA and PKC are part of the signaling pathway. This profile corresponds to the pharmacological signature of CFTR. 5: In the cystic fibrosis airway epithelial IB3-1 cell lacking functional CFTR but expressing VPAC1 receptors, neither VIP, PACAP-27 nor forskolin stimulated chloride transport. 6: Ussing chamber experiments demonstrated stimulation of CFTR-dependent short-circuit currents by VIP or PACAP-27 applied to the basolateral but not to the apical side of Calu-3 cells monolayers. 7: This study shows the stimulation in human bronchial epithelial cells of CFTR-dependent chloride secretion following activation by VIP and PACAP-27 of basolateral VPAC1 receptors.British Journal of Pharmacology (2004) 141, 698-708. doi:10.1038/sj.bjp.0705597 [ABSTRACT FROM AUTHOR]
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Activation of VPAC<subscript>1</subscript> receptors by VIP and PACAP-27 in human bronchial epithelial cells induces CFTR-dependent chloride secretion.
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Autor/in / Beteiligte Person: | Dérand, Renaud ; Montoni, Alicia ; Bulteau-Pignoux, Laurence ; Janet, Thierry ; Moreau, Bertrand ; Muller, Jean-Marc ; Becq, Frédéric |
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Zeitschrift: | British Journal of Pharmacology, Jg. 141 (2004-02-15), Heft 4, S. 698-708 |
Veröffentlichung: | 2004 |
Medientyp: | academicJournal |
ISSN: | 0007-1188 (print) |
DOI: | 10.1038/sj.bjp.0705597 |
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