Caffeine inhibits InsP3 responses and capacitative calcium entry in canine pulmonary arterial smooth muscle cells.
Caffeine inhibits InsP3 responses and capacitative calcium entry in canine pulmonary arterial smooth muscle cells.
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DOI：
10.1016/j.vph.2008.11.001
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发表时间：
2009-03
影响因子：
4
通讯作者：
Wilson, Sean M.
中科院分区：
文献类型：
--
作者：
Hume, Joseph R.;McAllister, Claire E.;Wilson, Sean M.
咖啡因是一种被充分描述和表征的兰尼碱受体（RyR）激活剂。来自独立研究的先前证据也表明咖啡因抑制InsP 3受体功能，这对某些细胞类型中的容量性Ca 2+进入（CCE）的激活很重要。此外，RyR激活eleventually兴奋性偶联钙离子内流（ECCE）在骨骼肌肌管。我们小组最近的研究表明，犬肺动脉平滑肌细胞（PASMC）具有功能性InsP 3受体和RyR，并且CCE依赖于InsP 3受体活性。在犬PASMCs中使用Fura-2荧光成像检查咖啡因激活ECCE以及抑制InsP 3受体功能和CCE的潜力。数据显示咖啡因引起短暂以及持续的胞质Ca 2+增加，尽管这不是由于CCE或ECCE活性，如通过缺乏Mn 2+淬灭fura-2的增加所证明的。实验还表明，咖啡因可逆地抑制5-HT引起的InsP 3介导的Ca 2+反应，IC 50为6.87 × 10−4 M，10 mM咖啡因完全抑制CCE。这些研究首次证明咖啡因是PASMCs中InsP 3产生的Ca ~（2+）信号和CCE的抑制剂。
Caffeine is a well described and characterized ryanodine receptor (RyR) activator. Previous evidence from independent research studies also indicate caffeine inhibits InsP3 receptor functionality, which is important to activation of capacitative Ca2+ entry (CCE) in some cell types. In addition, RyR activation elicits excitatory-coupled Ca2+ entry (ECCE) in skeletal muscle myotubes. Recent studies by our group show that canine pulmonary arterial smooth muscle cells (PASMCs) have functional InsP3 receptors as well as RyRs, and that CCE is dependent on InsP3 receptor activity. The potential for caffeine to activate ECCE as well as inhibit InsP3 receptor function and CCE was examined using fura-2 fluorescent imaging in canine PASMCs. The data show caffeine causes transient as well as sustained cytosolic Ca2+ increases, though this is not due to CCE or ECCE activity as evidenced by a lack of an increase in Mn2+ quench of fura-2. The experiments also show caffeine reversibly inhibits 5-HT elicited – InsP3 mediated Ca2+ responses with an IC50 of 6.87 × 10−4 M and 10 mM caffeine fully inhibits CCE. These studies provide the first evidence that caffeine is an inhibitor of InsP3 generated Ca2+ signals and CCE in PASMCs.
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气道平滑肌松弛是由于CAMP介导的IP3受体抑制引起的Ca2+振荡频率的降低而导致的。
影响因子：
5.8
作者：
Bai, Y;Sanderson, MJ
通讯作者：
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DOI：
10.1152/ajplung.00188.2005
发表时间：
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作者：
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DOI：
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发表时间：
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影响因子：
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DOI：
10.1152/ajplung.00449.2003
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影响因子：
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作者：
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影响因子：
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