Endothelin-1 inhibits mucin secretion from ovine airway epithelial goblet cells
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Endothelin-1 inhibits mucin secretion from ovine airway epithelial goblet cells. / Clancy, Sinead M; Yeadon, Michael; Parry, John; Yeoman, Mark S; Adam, Elizabeth C; Schumacher, Udo; Lethem, Michael I.
in: AM J RESP CELL MOL, Jahrgang 31, Nr. 6, 12.2004, S. 663-71.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Endothelin-1 inhibits mucin secretion from ovine airway epithelial goblet cells
AU - Clancy, Sinead M
AU - Yeadon, Michael
AU - Parry, John
AU - Yeoman, Mark S
AU - Adam, Elizabeth C
AU - Schumacher, Udo
AU - Lethem, Michael I
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
KW - Animals
KW - Endothelin-1
KW - Epithelial Cells
KW - Goblet Cells
KW - Immunohistochemistry
KW - Lectins
KW - Mucins
KW - Protein Binding
KW - Radioligand Assay
KW - Receptors, Endothelin
KW - Sheep
KW - Trachea
U2 - 10.1165/rcmb.2003-0331OC
DO - 10.1165/rcmb.2003-0331OC
M3 - SCORING: Journal article
C2 - 15347558
VL - 31
SP - 663
EP - 671
JO - AM J RESP CELL MOL
JF - AM J RESP CELL MOL
SN - 1044-1549
IS - 6
ER -