Document Detail


Endothelin-1 inhibits mucin secretion from ovine airway epithelial goblet cells.
MedLine Citation:
PMID:  15347558     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mucus hypersecretion is a feature of several respiratory diseases and frequently leads to obstruction of small airways where the principal source of mucous glycoproteins (mucins), the major macromolecular constituents of mucus, are goblet cells. Hence, inhibition of mucin secretion from these cells may be clinically beneficial. In this study, we have developed a lectin-based assay for mucin secretion from ovine airway goblet cells and used this assay to investigate the regulation of these cells by endothelin (ET)-1. ET-1 inhibited baseline mucin secretion (maximum inhibition: 60.3 +/- 4.2%, 50% inhibitory concentration: 0.8 +/- 0.17 nM). This response was abolished by the ET(A) antagonist, BQ-123 (1 muM), but not by the ET(B) antagonist, BQ-788 (1 muM). ET-1 (1 muM) did not affect mucin secretion stimulated by ATP (100 muM) but secretion in response to ATP (10 muM) was inhibited by 63.3 +/- 11.8%. This response could be eliminated by BQ-123, but not by BQ-788. Radioligand binding and immunohistochemistry indicated the expression of both ET(A)- and ET(B)-receptors on the epithelium. In summary, ET-1, acting via ET(A)-receptors, inhibits baseline and ATP-stimulated mucin secretion from ovine airway goblet cells. This represents the first report of a physiologic mechanism for inhibiting airway goblet cell mucin secretion; an understanding of this mechanism may provide opportunities for the treatment of obstructive airways disease.
Authors:
Sinead M Clancy; Michael Yeadon; John Parry; Mark S Yeoman; Elizabeth C Adam; Udo Schumacher; Michael I Lethem
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-09-03
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  31     ISSN:  1044-1549     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-19     Completed Date:  2005-01-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  663-71     Citation Subset:  IM    
Affiliation:
School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Endothelin-1 / antagonists & inhibitors,  pharmacology*
Epithelial Cells / drug effects*,  secretion
Goblet Cells / drug effects*,  secretion*
Immunohistochemistry
Lectins / pharmacology
Mucins / secretion*
Protein Binding
Radioligand Assay
Receptors, Endothelin / metabolism
Sheep
Trachea / cytology,  drug effects*,  metabolism,  secretion*
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Lectins; 0/Mucins; 0/Receptors, Endothelin

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