Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes
Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes
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DOI：
10.1007/s11302-009-9144-4
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发表时间：
2009-09-01
影响因子：
3.5
通讯作者：
Hauschildt, Sunna
中科院分区：
文献类型：
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作者：
Grahnert, Anja;Klein, Carina;Hauschildt, Sunna
在本研究中，我们发现细胞外添加烟酰胺腺嘌呤二核苷酸（NAD（+））诱导细胞外钙内流引起的人单核细胞[Ca 2 +]（i）的瞬时升高。NAD（+）诱导的Ca ~（2+）反应被三磷酸腺苷（ATP）阻断，提示ATP受体参与。在ATP受体的两种亚型（P2 X和P2 Y）中，P2 X受体被认为是最有可能的候选者。通过使用亚型优先激动剂和拮抗剂，我们鉴定了参与NAD（+）诱导的[Ca 2 +]（i）升高的P2 X（1）、P2 X（4）和P2 X（7）受体。在P2 X受体亚型中，P2 X（7）受体在促进非选择性孔的诱导方面是独特的，所述非选择性孔在用ATP刺激时允许乙锭进入。在单核细胞中，P2 X（7）受体依赖性孔的打开强烈依赖于特定的离子条件。测量响应于NAD（+）的孔形成，我们发现NAD（+）与ATP不同，缺乏诱导这种孔形成响应的能力。尽管低至100 μ M的ATP就足以激活非选择性孔，但浓度高达2 mM的NAD（+）没有作用。总而言之，这些数据表明，尽管细胞外NAD（+）和ATP的作用相似，但仍存在核苷酸特异性变异。到目前为止，人们才刚刚开始了解这两种核苷酸的共同特征和独特特征。
In the present study, we show that the extracellular addition of nicotinamide adenine dinucleotide (NAD(+)) induces a transient rise in [Ca2+](i) in human monocytes caused by an influx of extracellular calcium. The NAD(+)-induced Ca2+ response was prevented by adenosine triphosphate (ATP), suggesting the involvement of ATP receptors. Of the two subtypes of ATP receptors (P2X and P2Y), the P2X receptors were considered the most likely candidates. By the use of subtype preferential agonists and antagonists, we identified P2X(1), P2X(4), and P2X(7) receptors being engaged in the NAD(+)-induced rise in [Ca2+](i). Among the P2X receptor subtypes, the P2X(7) receptor is unique in facilitating the induction of nonselective pores that allow entry of ethidium upon stimulation with ATP. In monocytes, opening of P2X(7) receptor-dependent pores strongly depends on specific ionic conditions. Measuring pore formation in response to NAD(+), we found that NAD(+) unlike ATP lacks the ability to induce this pore-forming response. Whereas as little as 100 mu M ATP was sufficient to activate the nonselective pore, NAD(+) at concentrations up to 2 mM had no effect. Taken together, these data indicate that despite similarities in the action of extracellular NAD(+) and ATP there are nucleotide-specific variations. So far, common and distinct features of the two nucleotides are only beginning to be understood.