Chest ACCP Member Benefits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moore, P. E.
Right arrow Articles by Shore, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moore, P. E.
Right arrow Articles by Shore, S. A.
(Chest. 2003;123:368S-369S.)
© 2003 American College of Chest Physicians

Effect of Dexamethasone on ß2-Adrenergic Desensitization in Airway Smooth Muscle*

Role of the ARG19 Polymorphism

Paul E. Moore, MD; Mark M. Calder, BS; Eric S. Silverman; Reynold A. Panettieri, Jr., MD and Stephanie A. Shore, PhD

* From the Departments of Pediatrics and Pharmacology (Dr. Moore and Mr. Calder), Vanderbilt University School of Medicine, Nashville, TN; Physiology Program (Drs. Silverman and Shore), Harvard School of Public Health, Boston, MA; and Department of Medicine (Dr. Panettieri), University of Pennsylvania, Philadelphia, PA.

Correspondence to: Paul E. Moore, MD, Division of Pediatric Pulmonary Medicine, Vanderbilt University School of Medicine, 1161 21st Ave South, S0119 MCN, Nashville, TN 37232-2586

We examined the ability of the corticosteroid dexamethasone to inhibit short-term (1 h) and long-term (24 h) ß2-adrenergic desensitization in cultured human airway smooth muscle (HASM) cells. In cells from 19 individuals studied on 47 experimental days, pretreatment with isoproterenol at 10-7 mol/L for 1 h or 24 h caused approximately 21% and 77% decreases in the ability of subsequent isoproterenol (10-6 mol/L) stimulation to reduce HASM cell stiffness as measured by magnetic twisting cytometry, similar to results we have previously reported.1 We examined the ability of dexamethasone (10-6 mol/L) administered 6 h or 48 h prior to isoproterenol pretreatment, and stratified our results by presence or absence of the Arg19 allele of the ß2AR upstream peptide, located in the 5'-leader cistron of the ß2AR gene. This polymorphism has been associated with decreased ß2AR expression in HASM cells. In cells containing at least one Arg19 allele, dexamethasone did not significantly reverse short-term or long-term desensitization, but in cells without the Arg19 allele, dexamethasone significantly reversed short-term and long-term desensitization (35% and 31%, respectively; p < 0.05 for each). Our results suggest that the Arg19 allele, or other polymorphisms of the promoter of the ß2AR gene that are in linkage disequilibrium, may affect the ability of dexamethasone to upregulate ß2AR expression in HASM cells. In addition, our results suggest that ß2AR genotype may be predictive of corticosteroid responsiveness in individuals with asthma.


   Footnotes
 
Abbreviation: HASM = human airway smooth muscle

This abstract is supported by National Institutes of Health grants HL04395, HL56383, HL33009, and HL67663, and the American Lung Association.


   References
TOP
 References
 

  1. Moore, PE, Laporte, PD, Abraham, JH, et al (2000) Polymorphism of the ß2-adrenergic receptor gene and desensitization in human airway smooth muscle. Am J Respir Crit Care Med 162,2117-2124[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Proc Am Thorac SocHome page
M. L. Toews and D. B. Bylund
Pharmacologic Principles for Combination Therapy
Proceedings of the ATS, November 1, 2005; 2(4): 282 - 289.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moore, P. E.
Right arrow Articles by Shore, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moore, P. E.
Right arrow Articles by Shore, S. A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS