Title
Adenosine A1 receptors mediate mobilization of calcium in human bronchial smooth muscle cells
UMMS Affiliation
Department of Pulmonary Medicine
Publication Date
5-20-2006
Document Type
Article
Subjects
Adenosine-5'-(N-ethylcarboxamide); Biological Transport, Active; Bronchi; *Calcium Signaling; Cells, Cultured; Cyclic AMP; GTP-Binding Proteins; Humans; Myocytes, Smooth Muscle; Phosphotransferases (Alcohol Group Acceptor); Receptor, Adenosine A1; Signal Transduction
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Adenosine stimulates contraction of airway smooth muscle, but the mechanism is widely considered indirect, depending on release of contractile agonists from mast cells and nerves. The goal was to determine whether adenosine, by itself, directly regulates calcium signaling in human bronchial smooth muscle cells (HBSMC). Primary cultures of HBSMC from normal subjects were loaded with fura 2-AM, and cytosolic calcium concentrations ([Ca(2+)](i)) were determined ratiometrically by imaging single cells. The nonselective adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA), and the adenosine A(1) receptor agonist, N(6)-cyclopentyladenosine (CPA), both stimulated rapid, transient increases in [Ca(2+)](i). In contrast, there were no calcium responses to 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido-adenosine (100 nM) or N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (100 nM), selective agonists at adenosine A(2A) receptors and adenosine A(3) receptors, respectively. Calcium responses to NECA and CPA were inhibited by 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A(1) receptor antagonist, and by pertussis toxin (PTX). In other experiments, NECA stimulated calcium transients in the absence of extracellular calcium, but not when cells were preincubated in cyclopiazonic acid or thapsigargin to empty intracellular calcium stores. Calcium responses were attenuated by xestospongin C and 2-aminoethoxydiphenylborane, inhibitors of inositol trisphosphate (IP(3)) receptors, and by U73122, an inhibitor of phospholipase C. It was concluded that stimulation of adenosine A(1) receptors on HBSMC rapidly mobilizes intracellular calcium stores by a mechanism dependent on PTX-sensitive G proteins, and IP(3) signaling. These findings suggest that, in addition to its well-established indirect effects on HBSMC, adenosine also has direct effects on contractile signaling pathways.
DOI of Published Version
10.1165/rcmb.2005-0290OC
Source
Am J Respir Cell Mol Biol. 2006 Oct;35(4):496-502. Epub 2006 May 18. Link to article on publisher's site
Journal/Book/Conference Title
American journal of respiratory cell and molecular biology
Related Resources
PubMed ID
16709961
Repository Citation
Ethier, Michael F. and Madison, John M., "Adenosine A1 receptors mediate mobilization of calcium in human bronchial smooth muscle cells" (2006). Open Access Articles. 156.
https://escholarship.umassmed.edu/oapubs/156