Endothelin-1 inhibits mucin secretion from ovine airway epithelial goblet cells

American Journal of Respiratory Cell and Molecular Biology
Sinead M ClancyM I Lethem

Abstract

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 t...Continue Reading

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Citations

Oct 4, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jiri KalabisMeenhard Herlyn
Sep 2, 2010·Journal of Inflammation·Latasha AbeynaikeRobert J Bischof
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Aug 1, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Diane F LeeAlison B Lansley
Aug 31, 2021·International Journal of Pharmaceutics·Marwa M R R AyoubAlison B Lansley

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