Imipramine inhibition of TRPM-like plasmalemmal Mg2+transport in vascular smooth muscle cells
Imipramine inhibition of TRPM-like plasmalemmal Mg2+transport in vascular smooth muscle cells
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DOI：
10.1111/j.1582-4934.2010.01024.x
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发表时间：
2011-03-01
影响因子：
5.3
通讯作者：
Nakayama, Shinsuke
中科院分区：
文献类型：
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作者：
Hamaguchi, Yukihisa;Tatematsu, Yasushi;Nakayama, Shinsuke
抑郁症与血管疾病有关，如心肌梗死和中风。药物治疗可能有助于这种关联。另一方面，Mg 2+缺乏症也被认为是同一类疾病的危险因素。在本研究中，我们研究了丙咪嗪对血管平滑肌中镁离子稳态的影响，特别是通过美拉汀型瞬时受体电位（TRPM）样镁离子渗透通道。使用31 P-核磁共振（NMR）在表达TRPM 6和TRPM 7两者的猪颈动脉中测量细胞内游离Mg 2+浓度（[Mg 2 +]（i）），后者是主要的。同时监测pH（i）和细胞内磷化合物。为了排除Na+依赖性Mg 2+转运，并促进Mg 2+渗透通道的活性，在不存在Na+和Ca 2+的情况下进行实验。将细胞外Mg 2+浓度改变为0和6 mM分别以时间依赖性方式显著降低和增加[Mg 2 +]（i）。在无Na+和Ca 2+的条件下，丙咪嗪统计学上显著减弱了双向[Mg 2 +]（i）变化。这种抑制作用在流入中是相当的，并且在流出中比2-氨基乙氧基二苯基硼酸盐更有效，2-氨基乙氧基二苯基硼酸盐是一种众所周知的TRPM 7阻断剂，TRPM 7是一种在细胞Mg 2+稳态中起主要作用的通道。[ATP]（i）和pH（i）均与[Mg 2 +]（i）的变化无关。结果表明，丙咪嗪抑制Mg 2+渗透通道推测通过直接影响的通道域。这种抑制作用似乎有助于，至少部分地，抗抑郁药和血管疾病的风险之间的联系。
Depression is associated with vascular disease, such as myocardial infarction and stroke. Pharmacological treatments may contribute to this association. On the other hand, Mg2+ deficiency is also known to be a risk factor for the same category of diseases. In the present study, we examined the effect of imipramine on Mg2+ homeostasis in vascular smooth muscle, especially via melastatin-type transient receptor potential (TRPM)-like Mg2+-permeable channels. The intracellular free Mg2+ concentration ([Mg2+](i)) was measured using 31P-nuclear magnetic resonance (NMR) in porcine carotid arteries that express both TRPM6 and TRPM7, the latter being predominant. pH(i) and intracellular phosphorus compounds were simultaneously monitored. To rule out Na+-dependent Mg2+ transport, and to facilitate the activity of Mg2+-permeable channels, experiments were carried out in the absence of Na+ and Ca2+. Changing the extracellular Mg2+ concentration to 0 and 6 mM significantly decreased and increased [Mg2+](i), respectively, in a time-dependent manner. Imipramine statistically significantly attenuated both of the bi-directional [Mg2+](i) changes under the Na+- and Ca2+-free conditions. This inhibitory effect was comparable in influx, and much more potent in efflux to that of 2-aminoethoxydiphenyl borate, a well-known blocker of TRPM7, a channel that plays a major role in cellular Mg2+ homeostasis. Neither [ATP](i) nor pH(i) correlated with changes in [Mg2+](i). The results indicate that imipramine suppresses Mg2+-permeable channels presumably through a direct effect on the channel domain. This inhibitory effect appears to contribute, at least partially, to the link between antidepressants and the risk of vascular diseases.