Effects of exogenous nicotinamide adenine dinucleotide (NAD+) in the rat heart are mediated by P2 purine receptors.
Effects of exogenous nicotinamide adenine dinucleotide (NAD+) in the rat heart are mediated by P2 purine receptors.
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DOI：
10.1186/s12929-016-0267-y
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发表时间：
2016-06-27
影响因子：
11
通讯作者：
Abramochkin DV
中科院分区：
文献类型：
--
作者：
Kuzmin VS;Pustovit KB;Abramochkin DV
近年来，NAD+被认为是参与神经控制生理功能和细胞间通讯的重要因素。 NAD+ 也被认为是 P1 和 P2 嘌呤受体的内源性激活剂。细胞外 NAD+ 在心脏组织中的作用仍缺乏研究。本研究旨在探讨细胞外NAD+对不同类型大鼠室上和心室工作心肌的影响及其潜在机制。使用在心脏多细胞制剂中记录锐微电极动作电位的标准技术来研究 NAD+ 的作用。细胞外 NAD+ 诱导左心耳 (LA)、右心耳 (RA)、肺静脉 (PV) 和右心室壁 (RV) 心肌制剂的生物电活动发生显着变化。 10–100 μM NAD+ 在 LA 和 RA 中产生两种相反的作用——动作电位 (AP) 快速发展和短暂延长，以及在最初的积极作用之后延迟持续的 AP 缩短。在 PV 和 RV 中，仅观察到 AP 因 NAD+ 应用而缩短。在 PV 制剂中，NAD+ 诱导的 AP 缩短可被视为潜在的致心律失常作用。 NAD+ 的心肌作用很可能是由 P2 嘌呤受体介导的，因为 P1 阻断剂 DPCPX 未能影响它们，而 P2 拮抗剂苏拉明消除了 NAD + 诱导的电活动改变。 P2X受体可能负责NAD + -诱导的短暂AP延长，而P2Y受体介导持续AP缩短。 PLC 抑制剂 U73122 部分消除了后一种作用，表明磷酸肌醇信号通路可能参与 NAD+ 心肌作用的介导。细胞外 NAD+ 被认为是心脏电活动的新型调节剂。 P2 受体代表至少在大鼠心脏中 NAD+ 的主要靶标。
Recently, NAD+ has been considered as an essential factor, participating in nerve control of physiological functions and intercellular communication. NAD+ also has been supposed as endogenous activator of P1 and P2 purinoreceptors. Effects of extracellular NAD+ remain poorly investigated in cardiac tissue. This study aims to investigate the effects of extracellular NAD+ in different types of supraventricular and ventricular working myocardium from rat and their potential mechanisms. The standard technique of sharp microelectrode action potential recording in cardiac multicellular preparations was used to study the effects of NAD+. Extracellular NAD+ induced significant changes in bioelectrical activity of left auricle (LA), right auricle (RA), pulmonary veins (PV) and right ventricular wall (RV) myocardial preparations. 10–100 μM NAD+ produced two opposite effects in LA and RA – quickly developing and transient prolongation of action potentials (AP) and delayed sustained AP shortening, which follows the initial positive effect. In PV and RV only AP shortening was observed in response to NAD+ application. In PV preparations AP shortening induced by NAD+ may be considered as a potential proarrhythmic effect. Revealed cardiotropic effects of NAD+ are likely to be mediated by P2 purine receptors, since P1 blocker DPCPX failed to affect them and P2 antagonist suramin abolished NAD + −induced alterations of electrical activity. P2X receptors may be responsible for NAD + −induced short-lasting AP prolongation, while P2Y receptors mediate persistent AP shortening. The latter effect is partially removed by PLC inhibitor U73122 showing the potential involvement of phosphoinositide signaling pathway in mediation of NAD+ cardiotropic effects. Extracellular NAD+ is supposed to be a novel regulator of cardiac electrical activity. P2 receptors represent the main target of NAD+ at least in the rat heart.