NAADP-induced Ca2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae
NAADP-induced Ca2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae
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DOI：
10.1002/jcp.21407
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发表时间：
2008-08-01
影响因子：
5.6
通讯作者：
Filippini, Antonio
中科院分区：
文献类型：
--
作者：
Gambara, Guido;Billington, Richard A.;Filippini, Antonio
我们研究了NAADP介导的Ca ~（2+）动员在大鼠肾小管周围平滑肌细胞内皮素（ET）信号转导中通过内皮素受体亚型A（ETA）和内皮素受体亚型B（ET B）的作用。微量注射和细胞外应用NAADP都能引起Ca 2+释放，这是由抑制浓度的NAADP，通过损害Ca 2+摄取在酸性商店与巴夫洛霉素，和thapsigargin阻断。通过相同的策略抑制NAADP信号传导，消除了响应于选择性ETB刺激的Ca 2+释放，而这些治疗仅部分损害了ETA依赖性Ca 2+信号传导，表明ETB信号的转导依赖于NAADP。此外，我们表明，脂筏/小窝含有ETA，ETB，和NAADP/cADPR生成酶CD 38和ETB受体的刺激导致CD 38活性增加;有趣的是，ETB-（而不是ETA-）介导的Ca 2+反应被拮抗破坏脂筏/小窝与甲基-β-环糊精。这些数据表明，在ETB介导的Ca 2+信号的NAADP的主要作用，并强烈建议在触发ET诱导的NAADP信号的脂筏/小窝的新的作用。
We have investigated the role of NAADP-mediated Ca2+ mobilization in endothelin (ET) signaling via endothelin receptor subtype A (ETA) and endothelin receptor subtype B (ETB) in rat peritubular smooth muscle cells. Microinjection and extracellular application of NAADP were both able to elicit Ca2+ release which was blocked by inhibitory concentrations of NAADP, by impairing Ca2+ uptake in acidic stores with bafilomycin, and by thapsigargin. Ca2+ release in response to selective ETB stimulation was abolished by inhibition of NAADP signaling through the same strategies, while these treatments only partially impaired ETA-dependent Ca2+ signaling, showing that transduction of the ETB signal is dependent on NAADP. In addition, we show that lipid rafts/caveolae contain ETA, ETB, and NAADP/cADPR generating enzyme CD38 and that stimulation of ETB receptors results in increased CD38 activity; interestingly, ETB- (but not ETA-) mediated Ca2+ responses were antagonized by disruption of lipid rafts/caveolae with methyl-beta-cyclodextrin. These data demonstrate a primary role of NAADP in ETB-mediated Ca2+ signaling and strongly suggest a novel role of lipid rafts/caveolae in triggering ET-induced NAADP signaling.