2. Academic Validation
  3. Effects of (a Combination of) the Beta2-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction

Effects of (a Combination of) the Beta2-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction

  • Cells. 2021 May 18;10(5):1237. doi: 10.3390/cells10051237.
Harm Maarsingh 1,  Anouk Oldenburger 2 3 4,  Bing Han 2 3 4,  Annet B Zuidhof 2 3,  Carolina R S Elzinga 2 3,  Wim Timens 4 5,  Herman Meurs 2 3 4,  Ramadan B Sopi 2 3 6,  Martina Schmidt 2 3 4
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL 33416, USA.
  • 2 Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands.
  • 3 Groningen Research Institute of Pharmacy, University of Groningen, 9713 AW Groningen, The Netherlands.
  • 4 Groningen Research Institute of Asthma and COPD, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
  • 5 Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
  • 6 Department of Premedical Courses, Faculty of Medicine, University of Prishtina, 10000 Prishtina, Kosovo.
PMID: 34069899 DOI: 10.3390/cells10051237
Abstract

Expression of bronchodilatory β2-adrenoceptors and bronchoconstrictive muscarinic M3-receptors alter with airway size. In COPD, (a combination of) β2-agonists and muscarinic M3-antagonists (anticholinergics) are used as bronchodilators. We studied whether differential receptor expression in large and small airways affects the response to β2-agonists and anticholinergics in COPD. Bronchoprotection by indacaterol (β2-agonist) and glycopyrrolate (anticholinergic) against methacholine- and EFS-induced constrictions of large and small airways was measured in guinea pig and human lung slices using video-assisted microscopy. In guinea pig lung slices, glycopyrrolate (1, 3 and 10 nM) concentration-dependently protected against methacholine- and EFS-induced constrictions, with no differences between large and small intrapulmonary airways. Indacaterol (0.01, 0.1, 1 and 10 μM) also provided concentration-dependent protection, which was greater in large airways against methacholine and in small airways against EFS. Indacaterol (10 μM) and glycopyrrolate (10 nM) normalized small airway hyperresponsiveness in COPD lung slices. Synergy of low indacaterol (10 nM) and glycopyrrolate (1 nM) concentrations was greater in LPS-challenged guinea pigs (COPD model) compared to saline-challenged controls. In conclusion, glycopyrrolate similarly protects large and small airways, whereas the protective effect of indacaterol in the small, but not the large, airways depends on the contractile stimulus used. Moreover, findings in a guinea pig model indicate that the synergistic bronchoprotective effect of indacaterol and glycopyrrolate is enhanced in COPD.

Keywords

airway responsiveness; anticholinergic; chronic obstructive pulmonary disease; glycopyrrolate; glycopyrronium; guinea pig; human; indacaterol; large airways; small airways; β2-agonist.

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