Activation and inactivation of Ca2+ release by NAADP(+)
Activation and inactivation of Ca2+ release by NAADP(+)
复制标题
DOI：
10.1074/jbc.271.15.8513
复制
发表时间：
1996-04-12
影响因子：
4.8
通讯作者：
Lee, HC
中科院分区：
文献类型：
--
作者：
Aarhus, R;Dickey, DM;Lee, HC
烟酸腺嘌呤二核苷酸磷酸（NAADP（+））是最近鉴定的NADP（+）的代谢物，其在海胆卵和微粒体中动员细胞内Ca 2+方面与三磷酸肌醇（IP 3）和环ADP-核糖（cADPR）一样有效（Clapper，D. L.，Walseth，T. F.、达吉，P. J.，和Lee，H. C.（1987）J.Biol.Chem.262，9561-9568; Lee，H. C.的方法，和Aarhus，R.（1995）J. Biol，Chem，270，2152-2157）。NAADP（+）激活Ca 2+释放的机制及其作用的Ca 2+库与IP 3和cADPR不同。在本研究中，我们发现在完整的海胆卵中，光解笼状的NAADP（+）引起长时程的Ca ~（2+）振荡，另一方面，释放阈值量的NAADP（+）产生脱敏作用。在微粒体中，这种自失活机制表现出浓度和时间依赖性。结合研究表明，NAADP（+）受体与cADPR不同，在阈下浓度时，NAADP（+）能以时间依赖性方式完全阻断随后与受体的结合，因此，NAADP（+）敏感的Ca ~（2+）释放过程具有新的调节特征，其与由IP 3或cADPR介导的Ca 2+释放不同。这种释放机制的电池可以提供必要的多功能性细胞响应不同的信号，导致Ca 2+动员。
Nicotinic acid adenine dinucleotide phosphate (NAADP(+)) is a recently identified metabolite of NADP(+) that is as potent as inositol trisphosphate (IP3) and cyclic ADP-ribose (cADPR) in mobilizing intracellular Ca2+ in sea urchin eggs and microsomes (Clapper, D. L., Walseth, T. F., Dargie, P. J., and Lee, H. C. (1987) J. Biol. Chem. 262, 9561-9568; Lee, H. C., and Aarhus, R. (1995) J. Biol, Chem, 270, 2152-2157). The mechanism of Ca2+ release activated by NAADP(+) and the Ca2+ stores it acts on are different from those of IP3 and cADPR. In this study we show that photolyzing caged NAADP(+) in intact sea urchin eggs elicits long term Ca2+ oscillations, On the other hand, uncaging threshold amounts of NAADP(+) produces desensitization. In microsomes, this self-inac tivation mechanism exhibits concentration and time dependence, Binding studies show that the NAADP(+) receptor is distinct from that of cADPR, and at subthreshold concentrations, NAADP(+) can fully inactivate subsequent binding to the receptor in a time-dependent manner, Thus, the NAADP(+)-sensitive Ca2+ release process has novel regulatory characteristics, which are distinguishable from Ca2+ release mediated by either IP3 or cADPR. This battery of release mechanisms may provide the necessary versatility for cells to respond to diverse signals that lead to Ca2+ mobilization.