ATP stimulates Ca2+ oscillations and contraction in airway smooth muscle cells of mouse lung slices
ATP stimulates Ca2+ oscillations and contraction in airway smooth muscle cells of mouse lung slices
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DOI：
10.1152/ajplung.00139.2002
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发表时间：
2002-12-01
影响因子：
4.9
通讯作者：
Sanderson, MJ
中科院分区：
文献类型：
--
作者：
Bergner, A;Sanderson, MJ
在小鼠肺切片的气道平滑肌细胞(SMC)中，大于或等于10微米的三磷酸腺苷诱导伴随着呼吸道收缩的钙振荡。大约1分钟后，Ca~(2+)振荡减弱，气道松弛。相反，大于或等于0.5umA的腺苷5‘-O-(3-硫代三磷酸)(不可水解性)可引起SMC内的钙振荡和相关的呼吸道收缩，持续2分钟。腺苷5‘-O-(3-硫代三磷酸)诱导的钙振荡在无外钙条件下发生，但可被磷脂酶C抑制剂U-73122和肌醇1，4，5-三磷酸受体抑制剂xestospongin所阻断。腺苷、AMP和α，β-亚甲基三磷酸腺苷对气道管径无影响，各种核苷酸引起的收缩反应的大小顺序为：ATP=UTP>；ADP。这些结果表明，SMC对三磷酸腺苷的反应受三磷酸腺苷水解酶的影响，并通过P2Y(2)或P2Y(4)受体介导，激活磷脂酶C通过肌醇1，4，5-三磷酸受体释放钙离子。我们的结论是，ATP可以作为气道SMC的痉挛源，SMC中的钙振荡是维持气道收缩所必需的。
In airway smooth muscle cells (SMCs) from mouse lung slices, greater than or equal to10 muM ATP induced Ca2+ oscillations that were accompanied by airway contraction. After similar to1 min, the Ca2+ oscillations subsided and the airway relaxed. By contrast, greater than or equal to0.5 muM 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-(3-thiotriphosphate)- 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 alpha,beta-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 P2Y(2) or P2Y(4) 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.