NAADP receptors are present and functional in the heart
NAADP receptors are present and functional in the heart
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DOI：
10.1016/s0960-9822(01)00269-x
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发表时间：
2001-06-26
期刊：
影响因子：
9.2
通讯作者：
Genazzani, AA
中科院分区：
文献类型：
--
作者：
Bak, J;Billington, RA;Genazzani, AA
除了经过充分研究的肌醇 1,4,5 三磷酸和兰尼碱受体外，越来越多的证据表明，一种由吡啶核苷酸烟酸腺嘌呤二核苷酸磷酸 (NAADP) 门控的新细胞内释放机制存在于从植物到哺乳动物细胞的许多生物体中（综述见[1]）。大多数细胞已被证明表达至少两种由不同信使控制的 Ca2+ 释放机制，这可能导致反应的冗余、趋同或发散。肌肉和心脏收缩组织似乎是一个例外。在此，人们认为主要的细胞内通道是兰尼碱受体，而 IF 受体表达较差，其作用似乎可以忽略不计。我们现在报道，NAADP 受体在心脏微粒体中具有功能且丰富。 NAADP 以高亲和力（130 pM 和 4 nM）特异性结合至心脏微粒体上的两个位点，并释放 Ca2+，表观 EC50 为 323 +/- 14 nM。此外，结合实验表明该受体表现出正协同性和负协同性，这是细胞内 Ca2+ 通道中独一无二的特性。因此，我们表明心脏具有多种机制来增加 Ca2+ 信号传导的复杂性，并且 NAADP 可能是该器官功能中不可或缺的一部分。 (C) 2001 Elsevier Science Ltd. 保留所有权利。
Alongside the well-studied inositol 1,4,5 trisphosphate and ryanodine receptors, evidence is gathering that a new intracellular release mechanism, gated by the pyridine nucleotide nicotinic acid adenine dinucleotide phosphate (NAADP), is present in numerous organisms, ranging from plant to mammalian cells (reviewed in [1]), Most cells have been shown to express at least two Ca2+-release mechanisms controlled by different messengers, and this can lead to redundancy, convergence, or divergence of responses. One exception appears to be muscle and heart contractile tissues. Here, it is thought that the dominant intracellular channel is the ryanodine receptor, while IF, receptors are poorly expressed and their role appears to be negligible, We now report that NAADP receptors are functional and abundant in cardiac microsomes. NAADP binds specifically and with high affinity (130 pM and 4 nM) to two sites on cardiac microsomes and releases Ca2+ with an apparent EC50 of 323 +/- 14 nM, Furthermore, binding experiments show that this receptor displays both positive and negative cooperativity, a peculiarity unique among intracellular Ca2+ channels. Therefore, we show that the heart possesses multiple mechanisms to Increase the complexity of Ca2+ signaling and that NAADP may be integral in the functioning of this organ. (C) 2001 Elsevier Science Ltd. All rights reserved.