Effects of (a Combination of) the Beta<sub>2</sub>-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction
Expression of bronchodilatory β<sub>2</sub>-adrenoceptors and bronchoconstrictive muscarinic M<sub>3</sub>-receptors alter with airway size. In COPD, (a combination of) β<sub>2</sub>-agonists and muscarinic M<sub>3</sub>-antagonists (anticholinergics)...
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MDPI AG
2021-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/5/1237 |
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| author | Harm Maarsingh Anouk Oldenburger Bing Han Annet B. Zuidhof Carolina R. S. Elzinga Wim Timens Herman Meurs Ramadan B. Sopi Martina Schmidt |
| author_facet | Harm Maarsingh Anouk Oldenburger Bing Han Annet B. Zuidhof Carolina R. S. Elzinga Wim Timens Herman Meurs Ramadan B. Sopi Martina Schmidt |
| author_sort | Harm Maarsingh |
| collection | DOAJ |
| description | Expression of bronchodilatory β<sub>2</sub>-adrenoceptors and bronchoconstrictive muscarinic M<sub>3</sub>-receptors alter with airway size. In COPD, (a combination of) β<sub>2</sub>-agonists and muscarinic M<sub>3</sub>-antagonists (anticholinergics) are used as bronchodilators. We studied whether differential receptor expression in large and small airways affects the response to β<sub>2</sub>-agonists and anticholinergics in COPD. Bronchoprotection by indacaterol (β<sub>2</sub>-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. |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:19:02Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-5703f517814b4c94aeb70d034ab101942023-11-21T20:12:33ZengMDPI AGCells2073-44092021-05-01105123710.3390/cells10051237Effects of (a Combination of) the Beta<sub>2</sub>-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway ConstrictionHarm Maarsingh0Anouk Oldenburger1Bing Han2Annet B. Zuidhof3Carolina R. S. Elzinga4Wim Timens5Herman Meurs6Ramadan B. Sopi7Martina Schmidt8Department of Pharmaceutical Sciences, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL 33416, USADepartment of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The NetherlandsGroningen Research Institute of Asthma and COPD, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The NetherlandsExpression of bronchodilatory β<sub>2</sub>-adrenoceptors and bronchoconstrictive muscarinic M<sub>3</sub>-receptors alter with airway size. In COPD, (a combination of) β<sub>2</sub>-agonists and muscarinic M<sub>3</sub>-antagonists (anticholinergics) are used as bronchodilators. We studied whether differential receptor expression in large and small airways affects the response to β<sub>2</sub>-agonists and anticholinergics in COPD. Bronchoprotection by indacaterol (β<sub>2</sub>-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.https://www.mdpi.com/2073-4409/10/5/1237airway responsivenessanticholinergicβ<sub>2</sub>-agonistchronic obstructive pulmonary diseaseglycopyrrolateglycopyrronium |
| spellingShingle | Harm Maarsingh Anouk Oldenburger Bing Han Annet B. Zuidhof Carolina R. S. Elzinga Wim Timens Herman Meurs Ramadan B. Sopi Martina Schmidt Effects of (a Combination of) the Beta<sub>2</sub>-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction Cells airway responsiveness anticholinergic β<sub>2</sub>-agonist chronic obstructive pulmonary disease glycopyrrolate glycopyrronium |
| title | Effects of (a Combination of) the Beta<sub>2</sub>-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction |
| title_full | Effects of (a Combination of) the Beta<sub>2</sub>-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction |
| title_fullStr | Effects of (a Combination of) the Beta<sub>2</sub>-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction |
| title_full_unstemmed | Effects of (a Combination of) the Beta<sub>2</sub>-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction |
| title_short | Effects of (a Combination of) the Beta<sub>2</sub>-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction |
| title_sort | effects of a combination of the beta sub 2 sub adrenoceptor agonist indacaterol and the muscarinic receptor antagonist glycopyrrolate on intrapulmonary airway constriction |
| topic | airway responsiveness anticholinergic β<sub>2</sub>-agonist chronic obstructive pulmonary disease glycopyrrolate glycopyrronium |
| url | https://www.mdpi.com/2073-4409/10/5/1237 |
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