Document Detail

Force fluctuation-induced relengthening of acetylcholine-contracted airway smooth muscle.
MedLine Citation:
PMID:  18094087     Owner:  NLM     Status:  MEDLINE    
Superimposition of force fluctuations on contracted tracheal smooth muscle (TSM) has been used to simulate normal breathing. Breathing has been shown to reverse lung resistance of individuals without asthma and animals given methacholine to contract their airways; computed tomography scans also demonstrated bronchial dilation after a deep inhalation in normal volunteers. This reversal of airway resistance and bronchial constriction are absent (or much diminished) in individuals with asthma. Many studies have demonstrated that superimposition of force oscillations on contracted airway smooth muscle results in substantial smooth muscle lengthening. Subsequent studies have shown that this force fluctuation-induced relengthening (FFIR) is a physiologically regulated phenomenon. We hypothesized that actin filament length in the smooth muscle of the airways regulates FFIR of contracted tissues. We based this hypothesis on the observations that bovine TSM strips contracted using acetylcholine (ACh) demonstrated amplitude-dependent FFIR that was sensitive to mitogen-activated protein kinase (p38 MAPK) inhibition- an upstream regulator of actin filament assembly. We demonstrated latrunculin B (sequesters actin monomers thus preventing their assimilation into filaments resulting in shorter filaments) greatly increases FFIR and jasplakinolide (an actin filament stabilizer) prevents the effects of latrunculin B incubation on strips of contracted canine TSM. We suspect that p38 MAPK inhibition and latrunculin B predispose to shorter actin filaments. These studies suggest that actin filament length may be a key determinant of airway smooth muscle relengthening and perhaps breathing-induced reversal of agonist-induced airway constriction.
Richard W Mitchell; Maria L Dowell; Julian Solway; Oren J Lakser
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Proceedings of the American Thoracic Society     Volume:  5     ISSN:  1546-3222     ISO Abbreviation:  Proc Am Thorac Soc     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-20     Completed Date:  2008-03-07     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  101203596     Medline TA:  Proc Am Thorac Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  68-72     Citation Subset:  IM    
Section of Pulmonary and Critical Care Medicine, University of Chicago, MC6026, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
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MeSH Terms
Acetylcholine / pharmacology*
Actin Cytoskeleton / physiology
Asthma / drug therapy,  physiopathology
Bicyclo Compounds, Heterocyclic / pharmacology*
Depsipeptides / pharmacology*
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Muscle Contraction / drug effects,  physiology*
Muscle, Smooth / drug effects,  physiology*
Myosins / metabolism
Stress, Mechanical
Thiazoles / pharmacology*
Thiazolidines / pharmacology*
Grant Support
Reg. No./Substance:
0/Bicyclo Compounds, Heterocyclic; 0/Depsipeptides; 0/Thiazoles; 0/Thiazolidines; 102396-24-7/jasplakinolide; 51-84-3/Acetylcholine; 76343-94-7/latrunculin B; EC Protein Kinases; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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