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Am J Physiol Lung Cell Mol Physiol (August 2, 2002). doi:10.1152/ajplung.00139.2002
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Articles in PresS, published online ahead of print August 2, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00139.2002
Submitted on May 7, 2002
Accepted on July 31, 2002

Extracellular ATP stimulates calcium oscillations and contraction in airway smooth muscle cells of mice lung slices

Albrecht Bergner1 and Michael J. Sanderson1*

1 Department of Physiology, University of Massachusetts Medical School, Worcester, MA, USA

* To whom correspondence should be addressed. E-mail: Michael.Sanderson{at}umassmed.edu.

In mouse lung slices, ATP (>=10 µM) was found to induce Ca2+ oscillations in airway smooth muscle cells (SMCs) that were accompanied by airway contraction. After about 1 minute, the Ca2+ oscillations subsided and the airway relaxed. By contrast, ATP-{gamma}-s (non-hydrolysable, >= 0.5 µM) induced Ca2+ oscillations in the SMCs and an associated airway contraction that persisted for > 2 minutes. ATP-{gamma}-s-induced Ca2+ oscillations occurred in the absence of external Ca2+ but were abolished by the PLC inhibitor U73122 and the IP3-receptor inhibitor xestospongin. Adenosine, AMP, and {alpha}-ß-ME-ATP had no effect on airway caliber and the magnitude of the contractile response induced by a variety of nucleotides could be graded in the following order: ATP = UTP >> ADP. These results suggest that the SMC response to ATP is impaired by ATP-hydrolysis and mediated via P2Y2 or P2Y4 receptors activating PLC to release Ca2+ via the IP3-receptor. We conclude that ATP serves as a spasmogen of airway SMCs and that Ca2+ oscillations in SMCs are required to sustain airway contraction.




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