Nicotinic acid adenine dinucleotide phosphate mediates Ca2+ signals and contraction in arterial smooth muscle via a two-pool mechanism
Nicotinic acid adenine dinucleotide phosphate mediates Ca2+ signals and contraction in arterial smooth muscle via a two-pool mechanism
复制标题
DOI：
10.1161/01.res.0000047507.22487.85
复制
发表时间：
2002-12-13
影响因子：
20.1
通讯作者：
Evans, AM
中科院分区：
文献类型：
--
作者：
Boittin, FX;Galione, A;Evans, AM
先前对动脉平滑肌的研究表明，肌醇1,4,5-三磷酸（IP3）和环adp核糖从肌浆网调动Ca2+。相比之下，人们对烟酸腺嘌呤二核苷酸磷酸（一种源自β - nadp（+）的吡啶核苷酸）对Ca2+的动员知之甚少。我们在这里表明，细胞内透析的烟酸腺嘌呤二核苷酸磷酸（NAADP）诱导Ca2+释放的空间限制“爆发”，启动一个全球性的Ca2+波和收缩在肺动脉平滑肌细胞。分别用thapsigargin消耗肌浆网Ca2+储存和用ryanodine抑制ryanodine受体，NAADP阻断了全球Ca2+波。然而，在这些条件下，局部Ca2+爆发仍然被观察到。而IP3受体拮抗剂xestospongin C对NAADP介导的Ca2+信号没有影响。我们提出NAADP通过2池机制动员Ca2+，并且最初的Ca2+爆发被随后的肌浆网Ca2+释放放大，通过ryanodine受体，而不是通过IP3受体。
Previous studies of arterial smooth muscle have shown that inositol 1,4,5-trisphosphate (IP3) and cyclic ADP-ribose mobilize Ca2+ from the sarcoplasmic reticulum. In contrast, little is known about Ca2+ mobilization by nicotinic acid adenine dinucleotide phosphate, a pyridine nucleotide derived from beta-NADP(+). We show here that intracellular dialysis of nicotinic acid adenine dinucleotide phosphate (NAADP) induces spatially restricted "bursts" of Ca2+ release that initiate a global Ca2+ wave and contraction in pulmonary artery smooth muscle cells. Depletion of sarcoplasmic reticulum Ca2+ stores with thapsigargin and inhibition of ryanodine receptors with ryanodine, respectively, block the global Ca2+ waves by NAADP. Under these conditions, however, localized Ca2+ bursts are still observed. In contrast, xestospongin C, an IP3 receptor antagonist, had no effect on Ca2+ signals by NAADP. We propose that NAADP mobilizes Ca2+ via a 2-pool mechanism, and that initial Ca2+ bursts are amplified by subsequent sarcoplasmic reticulum Ca2+ release via ryanodine receptors but not via IP3 receptors.