Adenosine A1 receptors mediate mobilization of calcium in human bronchial smooth muscle cells.

Citation data:

American journal of respiratory cell and molecular biology, ISSN: 1044-1549, Vol: 35, Issue: 4, Page: 496-502

Publication Year:
2006
Usage 57
Abstract Views 57
Citations 39
Citation Indexes 39
Repository URL:
https://escholarship.umassmed.edu/oapubs/156
PMID:
16709961
DOI:
10.1165/rcmb.2005-0290oc
PMCID:
PMC2065849
Author(s):
Ethier, Michael F.; Madison, John M.
Publisher(s):
American Thoracic Society
Tags:
Medicine; Biochemistry, Genetics and Molecular Biology; 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; Life Sciences; Medicine and Health Sciences
article description
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.