Imperial College London

DrPankajBhavsar

Faculty of MedicineNational Heart & Lung Institute

Senior Research Fellow
 
 
 
//

Contact

 

p.bhavsar

 
 
//

Location

 

223Guy Scadding BuildingRoyal Brompton Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Shaikh:2017:10.2147/COPD.S134420,
author = {Shaikh, N and Johnson, M and Hall, D and Chung, KF and Riley, J and Worsley, S and Bhavsar, PK},
doi = {10.2147/COPD.S134420},
journal = {International Journal of Chronic Obstructive Pulmonary Disease},
pages = {1903--1913},
title = {Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle},
url = {http://dx.doi.org/10.2147/COPD.S134420},
volume = {12},
year = {2017}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background: Intracellular mechanisms of action of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a long-acting β2-adrenoceptor (β2R) agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs).Materials and methods: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh]). Cyclic adenosine monophosphate (cAMP) was measured using an enzyme-linked immunosorbent assay, intracellular free calcium ([Ca2+]i) using a fluorescence assay, and regulator of G-protein signaling 2 (RGS2) messenger RNA using real-time quantitative polymerase chain reaction.Results: VI and salmeterol (10–12–10–6 M) induced cAMP production from ASMCs in a concentration-dependent manner, which was greater for VI at all concentrations. β2R antagonism by propranolol or ICI 118.551 (10–12–10–4 M) resulted in concentration-dependent inhibition of VI-induced cAMP production, and ICI 118.551 was more potent. MCh (5×10–6 M, 30 minutes) attenuated VI-induced cAMP production (P<0.05), whereas pretreatment with UMEC (10–8 M, 1 hour) restored the magnitude of VI-induced cAMP production. ASMC stimulation with MCh (10–11–5×10–6 M) resulted in a concentration-dependent increase in [Ca2+]i, which was attenuated with UMEC pretreatment. Reduction of MCh-induced [Ca2+]i release was greater with UMEC + VI versus UMEC. UMEC enhanced VI-induced RGS2 messenger RNA expression.Conclusion: These data indicate that UMEC reverses cholinergic inhibition of VI-induced cAMP production, and is a more potent muscarinic receptor antagonist when in combination with VI versus either alone.
AU - Shaikh,N
AU - Johnson,M
AU - Hall,D
AU - Chung,KF
AU - Riley,J
AU - Worsley,S
AU - Bhavsar,PK
DO - 10.2147/COPD.S134420
EP - 1913
PY - 2017///
SN - 1176-9106
SP - 1903
TI - Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle
T2 - International Journal of Chronic Obstructive Pulmonary Disease
UR - http://dx.doi.org/10.2147/COPD.S134420
UR - http://hdl.handle.net/10044/1/48440
VL - 12
ER -