RT Journal Article
SR Electronic
T1 The effects of angiotensin II and related peptides on intracellular Ca2+ release in human lung fibroblasts
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3926
VO 42
IS Suppl 57
A1 Samantha Maitland
A1 Anthony Sampson
A1 Jane Warner
A1 David Hall
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P3926.abstract
AB Introduction. Fibroblasts are a key cell type responsible for the deposition of extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF). Angiotensin II (AngII) increases fibroblast proliferation and ECM deposition, but little is known about other angiotensin peptides, such as Ang(1-7), or their effects on fibroblasts.Aim. To determine the effects of angiotensin peptides on intracellular Ca2+ release in human lung fibroblasts (HLFs).Method. Eight angiotensin peptides were tested for their ability to mobilise calcium in HLFs using a FLIPR assay, and the EC50 calculated. Peptides that failed to mobilise Ca2+ were retested as antagonists.Results. AngI, AngII, AngIII and Ang(3-8) mobilised Ca2+ with EC50 values ranging from 22nM for AngII to >10μM for Ang(3-8). Telmisartan (10nM) completely abolished the Ca2+ response in all cases, indicating that all four peptides were acting via angiotensin receptor 1 (ATR1). Neither PD-123319 (ATR2 antagonist) nor A-779 (Ang(1-7) antagonist) had any effect on Ca2+ mobilisation. Pretreatment of the fibroblasts with 10μM Ang(1-7) or Ang(1-9) caused 43% and 60% inhibition of the maximal Ca2+ response to AngII respectively, with an IC50 of 2.9μM estimated for Ang(1-9) in this assay.Conclusion. Four angiotensin peptides generate a Ca2+ response in HLFs via ATR1; this Ca2+ release may influence functional responses such as proliferation and ECM deposition. Ang(1-7) and Ang(1-9) inhibit this calcium mobilisation in a manner that is not consistent with simple competitive antagonism; this mechanism of inhibition requires further investigation.