ATP stimulates Ca oscillations and contraction in airway smooth muscle cells of mouse lung slices

Bergner, Albrecht, and Michael J. Sanderson. ATP stimulates Ca2 oscillations and contraction in airway smooth muscle cells of mouse lung slices. Am J Physiol Lung Cell Mol Physiol 283: L1271–L1279, 2002. First published August 2, 2002; 10.1152/ajplung.00139.2002.—In airway smooth muscle cells (SMCs) from mouse lung slices, 10 M ATP induced Ca2 oscillations that were accompanied by airway contraction. After 1 min, the Ca2 oscillations subsided and the airway relaxed. By contrast, 0.5 M adenosine 5 -O-(3-thiotriphosphate) (nonhydrolyzable) induced Ca2 oscillations in the SMCs and an associated airway contraction that persisted for 2 min. Adenosine 5 -O-(3thiotriphosphate)-induced Ca2 oscillations occurred in the absence of external Ca2 but were abolished by the phospholipase C inhibitor U-73122 and the inositol 1,4,5-trisphosphate receptor inhibitor xestospongin. Adenosine, AMP, and , -methylene ATP had no effect on airway caliber, and the magnitude of the contractile response induced by a variety of nucleotides could be ranked 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 phospholipase C to release Ca2 via the inositol 1,4,5-trisphosphate receptor. We conclude that ATP can serve as a spasmogen of airway SMCs and that Ca2 oscillations in SMCs are required to sustain airway contraction.