N-Methyl-D-Aspartate Receptor Signaling and Function in Cardiovascular Tissues.
N-Methyl-D-Aspartate Receptor Signaling and Function in Cardiovascular Tissues.
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DOI：
10.1097/fjc.0000000000000398
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发表时间：
2016-08
影响因子：
3
通讯作者：
Abdel-Rahman AA
中科院分区：
文献类型：
--
作者：
McGee MA;Abdel-Rahman AA
中枢N-甲基-D-天冬氨酸受体（NMDAR）在心血管调节神经元库中的信号转导和功能已被大量报道。然而，很少有人关注NMDAR在外周组织，特别是心脏和血管系统中的功能，尽管最近的综述讨论了肾脏中的这种功能。本文就NMDAR在心血管组织中的表达及其功能的复杂性作一综述。在清醒（与麻醉相反）大鼠中，外周NMDAR的激活通过PI 3 K-ERK 1/2-NO信号通路触发心血管氧化应激，最终导致血压升高。证据还表明，在外周NMDAR介导的升压反应中，Ca 2+释放也有牵连。尽管存在循环有效配体（例如D-和L-天冬氨酸、L-高半胱氨酸和喹诺酮酸）以及它们的共激动剂（例如甘氨酸或D-丝氨酸）的证据，但外周心血管NMDAR的生理作用仍然难以捉摸。尽管如此，外周NMDAR的心血管相关性可能会变得明显，当其信号被药物改变时，如酒精，与NMDAR或其下游信号机制相互作用。
Excellent reviews on central N-methyl-D-Aspartate receptor (NMDAR) signaling and function in cardiovascular regulating neuronal pools have been reported. However, much less attention has been given to NMDAR function in peripheral tissues, particularly the heart and vasculature, although a very recent review discusses such function in the kidney. In this short review, we discuss the NMDAR expression and complexity of its function in cardiovascular tissues. In conscious (contrary to anesthetized) rats, activation of the peripheral NMDAR triggers cardiovascular oxidative stress via the PI3K-ERK1/2-NO signaling pathway, which ultimately leads to elevation in blood pressure. Evidence also implicates Ca2+ release, in the peripheral NMDAR-mediated pressor response. Despite evidence of circulating potent ligands (e.g. D- and L-aspartate, L-homocysteic acid and quinolonic acid) as well as their co-agonist (e.g. glycine or D-serine), the physiological role of peripheral cardiovascular NMDAR remains elusive. Nonetheless, the cardiovascular relevance of the peripheral NMDAR might become apparent when its signaling is altered by drugs, like alcohol, which interact with the NMDAR or its downstream signaling mechanisms.