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Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model.
- Source :
-
Scientific reports [Sci Rep] 2021 Sep 22; Vol. 11 (1), pp. 18828. Date of Electronic Publication: 2021 Sep 22. - Publication Year :
- 2021
-
Abstract
- Mucus clearance, a primary innate defense mechanism of airways, is defective in patients with cystic fibrosis (CF) and CF animals. In previous work, the combination of a low dose of the cholinergic agonist, carbachol with forskolin or a β adrenergic agonist, isoproterenol synergistically increased mucociliary clearance velocity (MCCV) in ferret tracheas. Importantly, the present study shows that synergistic MCCV can also be produced in CF ferrets, with increases ~ 55% of WT. Synergistic MCCV was also produced in pigs. The combined agonists increased MCCV by increasing surface fluid via multiple mechanisms: increased fluid secretion from submucosal glands, increased anion secretion across surface epithelia and decreased Na <superscript>+</superscript> absorption. To avoid bronchoconstriction, the cAMP agonist was applied 30 min before carbachol. This approach to increasing mucus clearance warrants testing for safety and efficacy in humans as a potential therapeutic for muco-obstructive diseases.<br /> (© 2021. The Author(s).)
- Subjects :
- Animals
Carbachol administration & dosage
Colforsin administration & dosage
Disease Models, Animal
Drug Synergism
Drug Therapy, Combination
Ferrets
Isoproterenol administration & dosage
Muscle Contraction drug effects
Muscle, Smooth drug effects
Swine
Carbachol therapeutic use
Colforsin therapeutic use
Cystic Fibrosis drug therapy
Isoproterenol therapeutic use
Mucociliary Clearance drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 34552115
- Full Text :
- https://doi.org/10.1038/s41598-021-98122-5